interleukin-8 and Dermatitis

It has been well established that cytidine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) activate innate and adaptive immune responses in keratinocytes by stimulating Toll-like receptor 9 (TLR9)-dependent signaling pathways. However, as Dorn et al. report, keratinocytes possess another, yet uncharacterized, TLR9-independent mechanism for the recognition of ODNs. Surprisingly, the activation of the pathway leads to suppressed chemokine production in vitro and decreased skin inflammation in vivo.

Topics: Animals; Chemokines; Dermatitis; Humans; Immunity, Innate; Interleukin-8; Keratinocytes; Oligodeoxyribonucleotides; Oligonucleotides; Toll-Like Receptor 9

Neutrophil infiltration into inflammatory sites is one of the hallmarks of acute inflammation. Locally produced chemotactic factors are presumed to mediate the sequence of events leading to the infiltration at inflammatory sites. Interleukin-8 (IL-8), a novel leukocyte chemotactic activating cytokine (chemokine), is produced by various types of cells upon stimulation with inflammatory stimuli and exerts a variety of functions on leukocytes, particularly, neutrophils in vitro. However, no definitive evidence has been presented on its role in recruiting and activating neutrophils in the lesions of various types of inflammatory reactions. We administered a highly specific neutralizing antibody against IL-8 in several types of acute inflammatory reactions, including lipopolysaccharide (LPS)-induced dermatitis, LPS/IL-1-induced arthritis, lung reperfusion injury, and acute immune complex-type glomerulonephritis. Anti-IL-8 treatment prevented neutrophil-dependent tissue damage as well as neutrophil infiltration in these conditions. These results suggest that IL-8 plays a causative role in acute inflammation by recruiting and activating neutrophils.

Topics: Animals; Antibodies; Antigen-Antibody Complex; Arthritis; Cross Reactions; Dermatitis; Glomerulonephritis; Inflammation; Inflammation Mediators; Interleukin-1; Interleukin-8; Lipopolysaccharides; Lung Diseases; Neutrophil Activation; Neutrophils; Rabbits; Reperfusion Injury

In the last decade a number of proteinaceous inflammatory mediators have been structurally characterized. Two of these mediators, tumor necrosis factor alpha (TNF alpha) and Interleukin 1 alpha and beta (IL-1), have pleiotropic properties. Both cytokines are now known to be potent inducers of a number of cell-selective chemotactic cytokines, which belong to a novel superfamily of structurally related low-molecular-weight proteins. One of the most prominent members is termed "IL-8" and represents a neutrophil-selective attractant, whereas another one called "monocyte chemotactic protein 1 (MCP-1)" is a monocyte-selective chemotaxin. Other members seem to be selective chemotaxins for other leukocyte types and subsets. These chemotactic cytokines are produced by a variety of different cells under appropriate stimulation conditions. Large amounts of IL-8 have been detected in scales of psoriatic lesions and may be of importance in explaining predominant neutrophil infiltration in psoriatic lesions. Regulation of gene expression and/or release of these chemotactic cytokines may occur by IL-1 receptor antagonists or soluble TNF-alpha-receptors. So far, natural antagonists to these chemotactic cytokines have not been described; however, pharmacological inhibition of its gene expression and/or release is possible.

Topics: Amino Acid Sequence; Animals; Chemokine CCL2; Chemotactic Factors; Cytokines; Dermatitis; Gene Expression; Humans; Interleukin-8; Molecular Sequence Data; Tumor Necrosis Factor-alpha

Cytokines (hormone-like polypeptide mediators) play a major role in inflammatory and immunoregulatory responses. Skin, and particularly keratinocytes in the skin, represent a potent source for many cytokines, including interleukins 1, 6, 8, and the hemopoietic colony stimulating factors. Cytokines initiate their biologic action by interacting with target cells bearing cytokine receptors and then initiating a cascade of cellular interactions. Certain inflammatory skin diseases have been associated with overproduction of cytokines, alteration in cytokine receptors, or dysregulation of cytokines. While data is still quite preliminary, it is likely that cytokines contribute to the pathogenesis of many inflammatory skin diseases.

Topics: Cytokines; Dermatitis; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Keratinocytes; Skin

Topics: Animals; Bone Marrow Cells; Chemotactic Factors; Chemotactic Factors, Eosinophil; Cytoplasmic Granules; Dermatitis; Histamine; Humans; Interleukin-8; Lysophosphatidylcholines; Mast Cells; Mitosis; Muscle Contraction; Muscle, Smooth; Nucleotides, Cyclic; Platelet Activating Factor; Proteoglycans; Rats; SRS-A

Psoriasis is a chronic inflammatory skin disease in which epidermal hyperplasia results from the release of cytokines by infiltrating type 1 T cells. Up- regulation of endogenous interleukin-10 controls type 1 skin responses in animal models; however, interleukin-10 production is low in psoriatic lesions. Consistent with an important role of interleukin-10 in psoriasis, we and colleagues have recently demonstrated clinical efficacy of subcutaneous administration of recombinant interleukin-10 to affected patients. Here, we studied the effects of interleukin-10 on disease-related inflammatory pathways. Patients were treated with recombinant interleukin-10 over 6 wk in an open-label phase II clinical trial. Tissue was obtained before and after therapy and examined by histology/immunohistochemistry, in situ hybridization, and quantitative real-time reverse transcription-polymerase chain reaction. Ten of 14 patients showed a marked reduction of the clinical disease activity. The clinical response was associated with a significant decrease of cutaneous T cell infiltration and the lesional expression of type 1 cytokines interferon-gamma and tumor necrosis factor-alpha. Interleukin-10 inhibited the epidermal interleukin-8 pathway by downregulating the expression of interleukin-8, its receptor CXCR2, and its inducer interleukin-17, and partially reversed the aberrant keratinocyte maturation defining psoriatic epidermal pathology. Remarkably, there was evidence that genetic factors are involved in the response to interleukin-10 as individual variations in the downregulation of tumor necrosis factor-alpha were related to the presence of polymorphisms in the tumor necrosis factor-alpha promoter. These data suggest that excessive production of type 1 cytokines in human skin disease can be counter-regulated by the administration of recombinant interleukin-10. Genotypic analysis may help to identify patients that will preferentially respond to interleukin-10 therapy.

Topics: Cell Differentiation; Cell Division; Cytokines; Dermatitis; Down-Regulation; Epidermis; Female; Humans; Interleukin-10; Interleukin-8; Keratinocytes; Male; Polymorphism, Genetic; Promoter Regions, Genetic; Psoriasis; Receptors, Interleukin-8B; Signal Transduction; Skin; T-Lymphocytes; Tumor Necrosis Factor-alpha

In this report, we provide a case of self-limiting canine acute febrile sterile neutrophilic dermatosis in which the clinical signs featured typical target skin lesions with strong upregulation of T-helper 1 markers and interleukin-8, a potent neutrophil chemoattractant. Further, large case series are needed to characterize canine sterile neutrophilic dermatosis.. Dans cet article, nous présentons un cas de dermatose neutrophilique fébrile stérile aiguë canine spontanément résolutive dans laquelle les signes cliniques comportaient des lésions cutanées cibles typiques avec une forte régulation à la hausse des marqueurs T-helper 1 et de l'interleukine-8, un puissant chimioattractant des neutrophiles. D'autres grandes séries de cas sont nécessaires pour caractériser la dermatose neutrophile stérile canine.. En este artículo exponemos un caso de dermatosis neutrofílica estéril febril aguda canina autolimitante en la que los signos clínicos fueron lesiones cutáneas típicas en forma de diana con una intensa elevación de los marcadores T-helper 1 y de interleucina-8, un potente quimiotáctico de neutrófilos. Se necesitan series de casos más grandes para caracterizar la dermatosis neutrofílica estéril canina.. In diesem Bericht beschreiben wir einen Fall selbst-limitierender fieberhafter neutrophiler Dermatose bei einem Hund, wobei die klinischen Zeichen aus typischen Target Hautläsionen mit starker Hochregulierung von T-Helfer 1 Marker und Interleukin-8, welches ein potentes neutrophiles Chemoattractant darstellt, bestanden. Weitere große Fallstudien sind nötig, um die canine sterile neutrophile Dermatose zu charakterisieren.. 本報告では、T-helper 1マーカーおよび好中球誘引物質であるインターロイキン-8の強い発現を伴う典型的な標的皮膚病変を呈した自己限定性犬急性発熱性無菌性好中球性皮膚症の1例を紹介する。犬の無菌性好中球性皮膚症の特徴を明らかにするためには、さらなる大規模なケースシリーズが必要である。.. 在本报告中，我们提供了一例自限性犬急性发热性无菌性中性粒细胞皮肤病，其临床症状表现为典型的靶样皮肤病变，辅助性 T 细胞1标记物和白细胞介素-8(一种强效中性粒细胞趋化因子)明显上调。需要进一步的大规模病例系列来表征犬无菌性中性粒细胞皮肤病。.. Neste relato, nós apresentamos um caso de dermatose neutrofílica estéril canina aguda febril em que os sinais clínicos típicos foram lesões cutâneas em alvo com forte ativação de marcadores T-helper 1 e interleucina-8, um potente quimioatrativo de neutrófilos. São necessários mais estudos com uma grande série de casos para caracterizar a dermatose neutrofílica estéril canina.

Topics: Animals; Dermatitis; Dog Diseases; Dogs; Interleukin-8; Neutrophils; Skin Diseases; Sweet Syndrome; Up-Regulation

A cow skin explants model was established to elucidate the mechanism of. Cow intertoe skin explants were cultured. The intertoe skin structure of cows infected with

Topics: Animals; Cattle; Cytokines; Dermatitis; Female; Foot Rot; Fusobacterium necrophorum; Inflammation; Interleukin-8; NF-kappa B; Signal Transduction; Tumor Necrosis Factor-alpha

The main function of sebocytes is considered to be the production of lipids to moisturize the skin. However, it recently became apparent that sebocytes release chemokines and cytokines and respond to proinflammatory stimuli as well as the presence of bacteria.. To analyse the functional communication between human sebocytes and T cells.. Immunofluorescence stainings for CD4 and interleukin (IL)-17 were performed on acne sections and healthy skin. Migration assays and T-cell-stimulation cultures were performed with supernatants derived from unstimulated or prestimulated SZ95 sebocytes. Dendritic cells were generated in the presence of SZ95 supernatant and subsequently used in mixed leucocyte reactions.. We showed that CD4. Our study provides evidence that human sebocytes actively participate in inflammatory processes in the skin by recruiting and communicating with immune cells. This interaction leads to the generation of Th17 cells, which might contribute to the pathogenesis not only of acne vulgaris, but also of several inflammatory skin diseases.

Topics: Cell Communication; Cell Differentiation; Cells, Cultured; Dermatitis; Humans; Immunity, Cellular; Interleukin-1beta; Interleukin-8; Langerhans Cells; Propionibacterium acnes; Sebaceous Glands; Th17 Cells

C-reactive protein (CRP) is a prototypic acute phase protein which increases dramatically in the blood during the first 48h of tissue inflammation and has been recognized as a risk factor for atherosclerosis. CRP interacts with a variety of proteins.. To know the role of accumulated CRP in the skin.. Interaction of CRP with basal keratinocytes was studied using immunohistochemical method and keratinocyte culture system.. We found an immunohistochemical deposition of CRP on the basal keratinocyte membrane in some normal human skins (23 out of 46 skins). When added to cultured keratinocytes, heat-denatured but not native CRP was found to adhere to keratinocyte cell membrane after 1h, then internalized into cytoplasm after 24h. The heat-denatured CRP recognized at least four keratinocyte polypeptides with the molecular weights of 56, 42, 32 and 24kDa. Ligand binding assays suggested that multiple populations of receptor-ligand interactions were involved in the binding between CRP and keratinocyte. Cultured dermal microvascular endothelial cells were found to express CRP of which expression was greatly induced by interleukin-1β (IL-1β) treatment, suggesting that the deposited CRP in the basal keratinocytes can be derived from local dermal microvasculatures as well as from systemic circulation (serum). Treatment of cultured keratinocytes with heat-denatured CRP induced interleukin-8 (IL-8) expression, a potent leukocyte chemotactic cytokine. CRP in the medium (liquid phase) and CRP-coated dishes (solid phase) both inhibited the adhesion of keratinocytes in culture.. Accumulation of CRP may regulate the skin inflammation and keratinocyte proliferation by modulating keratinocyte cytokine expression and adhesion to substrate.

Topics: C-Reactive Protein; Cell Adhesion; Cell Proliferation; Cells, Cultured; Dermatitis; Epidermis; Humans; Immunohistochemistry; Interleukin-1beta; Interleukin-8; Keratinocytes; Microvessels

The aim of this study is to develop the Tripterygium glycosides nanoemulsion gels and investigate its pharmacodynamics. Oleic acid was used as oil phase, polyoxyethylene castor oil as surfaetant, and 1,2-propanediol as cosurfactant to screen the formula of Tripterygium glycoside nanoemulsion using the pseudo-temary phase diagrams. Then the nanoemulsion gels was prepared. The ICR mouse ears were sensitazated by 7% DNCB, and then were excited by 0.3% DNCB to stimulate the model of mouse chronic dermatitis and eczema. The concentrations of IFN-γ, IL-4 and IL-8 in mouse blood were determined by ELISA. The results showed that Tripterygium glycosides nanoemulsion gels could significantly inhibit the swelling of mouse ears(P < 0.01) and ameliorate the edama and erythema of model mouse ears skin. Also it could significantly decrease the expression of IFN-γ and IL-4 in model mouse blood. Tripterygium glycosides nanoemulsion gels had a good therapeutic effect on mouse model of dermatitis and eczema. It was expected to provide a new and long-acting exterernal preparation for the treatment of dermatitis and eczema.

Topics: Animals; Chemistry, Pharmaceutical; Dermatitis; Drug Carriers; Drugs, Chinese Herbal; Emulsions; Female; Glycosides; Humans; Interleukin-4; Interleukin-8; Mice; Mice, Inbred ICR; Nanoparticles; Tripterygium

Occupational skin symptoms are prevalent among the workers of the seafood processing industry. In this study we investigate the role of salmon (Salmo salar) and king crab trypsin (Paralithodes camtschaticus) as inducers of inflammation in skin via secretion of inflammatory mediators. Human skin keratinocytes (HaCaT cells) were exposed to purified salmon and king crab trypsin. We observed that salmon trypsin enhanced the secretion of IL-8 and MMP-2 and crab trypsin enhanced the secretion of IL-8, MMP-2 and MMP-9 in a dose dependent manner. As protease activated receptors (PAR)-2 in skin are known to play an important role in physiology and pathology, we explored the involvement of these receptors in mediating the release of interleukin (IL)-8 and matrix metalloproteinase (MMP)-2 and -9 subsequent to exposure of skin keratinocytes to salmon and crab trypsin. In addition we observed that salmon and crab trypsin exhibit individual differences in stimulating the release of these inflammatory mediators. Finally, using specific small interfering RNA (siRNA) against PAR-2, we confirmed that the increase in secretion of IL-8, MMP-2 and MMP-9 in skin keratinocytes following exposure to salmon and crab trypsin was mediated via activation of PAR-2. These results suggest that exposure to proteases from the seafood may lead to inflammatory reactions in skin.

Topics: Animals; Anomura; Cell Line; Dermatitis; Humans; Interleukin-8; Keratinocytes; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Oligopeptides; Receptor, PAR-2; Salmon; Skin; Trypsin

Digital Dermatitis (DD) is a common disease of dairy cows, the pathogenesis of which is still not clear. This study examined some host responses associated with the typical lesions, in an attempt to further elucidate the pathogenesis of the disease. Twenty four samples representing the 5 different clinical stages of DD (M0-M4) were collected from slaughtered cattle for histopathological and immunological analyses.. Significant increases in total epidermal thickness were found in M2, M3, and M4 when compared with M0 and M1. M3 samples, when compared with M0 and M1, were characterized by a significant increase in the thickness of the keratin layer. Counts of both eosinophils and neutrophils were at a maximum in the M2 stage and decreased in the M3 and M4 stage. A significant increase in IL8 expression was observed in the M2-M3 stages of the disease and immunohistochemical staining showed the source as keratinocytes, suggesting an important role for keratinocyte-derived IL8 in the pathogenesis of DD.. Results of the present study point to a strong stimulation of the innate immune response at the level of the keratinocytes throughout most of the clinical stages, and a delayed response of the adaptive immune reaction.

Topics: Animals; Cattle; Cattle Diseases; Cloning, Molecular; Dermatitis; DNA, Complementary; Eosinophils; Female; Foot Diseases; Gene Expression Regulation; Immunity, Innate; Interleukin-8; Keratinocytes; Lymphocytes; Neutrophils; Real-Time Polymerase Chain Reaction; RNA

  Retinoids have been used for the treatment of skin disorders such as acne, psoriasis, and photoaging. However, despite their beneficial effects, topical retinoids often cause severe local irritation called retinoid dermatitis. We previously developed a novel vitamin A derivative, retinyl retinoate, which induces less irritation and affords excellent tolerance. In this study, we examined whether co-treatment with topical peroxisome proliferator-activated receptor-α (PPARα) agonists (e.g. WY14643) reduce retinoid dermatitis in hairless mouse skin..   The effect of concomitant treatment with a PPARα agonist on retinoid dermatitis in hairless mouse epidermis was evaluated by measuring transepidermal water loss, epidermal histology, and cytokine expression..   Retinyl retinoate induced less severe retinoid dermatitis than retinoic acid. Topical application of a PPARα agonist improved the stratum corneum structure and function, reduced mRNA expression of interleukin (IL)-1α, tumor necrosis factor-α and IL-8, and inhibited ear edema induced by retinoic acid or retinyl retinoate..   Our results indicate that PPARα agonists can potentially be used to improve retinoid dermatitis. We suggest that co-treatment with retinyl retinoate and a PPARα agonist may reduce or prevent detrimental alterations in retinoid-treated skin.

Topics: Administration, Topical; Animals; Cell Differentiation; Cell Proliferation; Dermatitis; Enzyme Inhibitors; Epidermis; Female; Interleukin-1alpha; Interleukin-8; Keratolytic Agents; Liver X Receptors; Mice; Mice, Hairless; Orphan Nuclear Receptors; Palmitic Acid; PPAR alpha; Pyrimidines; Retinoids; Retinyl Esters; RNA, Messenger; Tretinoin; Tumor Necrosis Factor-alpha; Water Loss, Insensible

Hippophae rhamnoides has been extensively used in oriental traditional medicines for treatment of asthma, skin diseases, gastric ulcers, and lung disorders. In this study, we isolated casuarinin from the leaves of H.rhamnoides and examined the effect of casuarinin on the TNF-α-induced ICAM-1 expression in a human keratinocytes cell line HaCaT. Pretreatment with casuarinin inhibited TNF-α-induced protein and mRNA expression of ICAM-1 and subsequent monocyte adhesiveness in HaCaT cells. Casuarinin significantly inhibited TNF-α-induced NF-κB activation. In addition, casuarinin inhibited activation of ERK and p38 MAPK in a dose-dependent manner. Furthermore, pretreatment with casuarinin decreased TNF-α-induced pro-inflammatory mediators, such as IL-1β, IL-6, IL-8, and MCP-1. These results demonstrated that casuarinin exerts its anti-inflammatory activity by suppressing TNF-α-induced expression of ICAM-1 and pro-inflammatory cytokines/chemokines via blockage of activation of NF-κB and ERK/p38 MAPK and can be used as a therapeutic agent against inflammatory skin diseases.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Chemokine CCL2; Dermatitis; Hippophae; Humans; Hydrolyzable Tannins; Intercellular Adhesion Molecule-1; Interleukin-1beta; Interleukin-6; Interleukin-8; Keratinocytes; NF-kappa B; Plant Leaves; Tumor Necrosis Factor-alpha

Proliferation and differentiation of keratinocytes are central processes in tissue regeneration after injury. Chemokines, produced by a wide range of cell types including keratinocytes, play a regulatory role in inflammatory skin diseases. Several studies have shown that an electromagnetic field (EMF) can influence both inflammatory processes and repair mechanisms including wound healing on different tissue models.. To elucidate the effect of extremely low frequency EMF (ELF-EMF) on keratinocyte proliferation and production of chemokines [RANTES, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1 alpha and interleukin (IL)-8] in order to evaluate a potential therapeutic use of magnetic fields.. The human keratinocyte cell line HaCaT was exposed at 1 mT, 50 Hz for different lengths of time and compared with unexposed control cells. Cell growth and viability were evaluated at different exposure times by cell count and trypan blue exclusion. Chemokine production and expression were analysed by enzyme-linked immunosorbent assay (ELISA) and by real-time polymerase chain reaction. Total NF-kappaB p65 was quantified by ELISA.. Significantly increased growth rates were observed after 48 h of EMF exposure as compared with control cells, while no difference in cell viabilities were detected. Gene expression and release of RANTES, MCP-1, MIP-1 alpha and IL-8 were significantly reduced after 72 h of exposure. NF-kappaB levels became almost undetectable after only 1 h of EMF exposure, and were inversely correlated with cell density.. Our results show that ELF-EMF modulates chemokine production and keratinocyte growth through inhibition of the NF-kappaB signalling pathway and thus may inhibit inflammatory processes. ELF-EMF could represent an additional therapeutic approach in the treatment of skin injury.

Topics: Cell Proliferation; Chemokine CCL5; Chemokines; Dermatitis; Dose-Response Relationship, Radiation; Electromagnetic Fields; Enzyme-Linked Immunosorbent Assay; Gene Expression; Humans; Interleukin-8; Keratinocytes; NF-kappa B; Reverse Transcriptase Polymerase Chain Reaction; Treatment Outcome; Wound Healing

Propionibacterium acnes is a key pathogen involved in the progression of inflammation in acne vulgaris. We examined whether vaccination against P. acnes suppressed P. acnes-induced skin inflammation. Inactivation of P. acnes with heat was employed to create a P. acnes-based vaccine. Intranasal immunization in mice with this inactivated vaccine provoked specific antibodies against P. acnes. Most notably, immunization with inactivated vaccines generated in vivo protective immunity against P. acnes challenge and facilitated the resolution of ear inflammation in mice. In addition, antibodies elicited by inactivated vaccines effectively neutralized the cytotoxicity of P. acnes and attenuated the production of proinflammatory cytokine IL-8 in human sebocyte SZ95 cells. Intranasal immunization using heat-inactivated P. acnes-based vaccines provided a simple modality to develop acne vaccines. These observations highlight the concept that development of vaccines targeting microbial products may represent an alternative strategy to conventional antibiotic therapy.

Topics: Acne Vulgaris; Animals; Antibodies, Bacterial; Bacterial Vaccines; Cell Line; Dermatitis; Female; Gram-Positive Bacterial Infections; Humans; Interleukin-8; Mice; Mice, Inbred ICR; Propionibacterium acnes; Sebaceous Glands; Vaccination; Vaccines, Inactivated

Topics: Cell Survival; Cells, Cultured; Dermatitis; Dose-Response Relationship, Drug; Humans; Immunosuppressive Agents; Interleukin-6; Interleukin-8; Keratinocytes; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Tacrolimus; Ultraviolet Rays

Transgenic mice overexpressing PKCalpha in the epidermis (K5-PKCalpha mice) exhibit an inducible severe intraepidermal neutrophilic inflammation and systemic neutrophilia when PKCalpha is activated by topical 12-O-tetradecanoylphorbol-13-acetate (TPA). This inducible model of cutaneous inflammation was used to define mediators of skin inflammation that may have clinical relevance. Activation of cutaneous PKCalpha increased the production of the chemotactic factors cytokine-induced neutrophil chemoattractant (KC) and macrophage inflammatory protein 2 (MIP-2) in murine plasma. TPA treatment of cultured K5-PKCalpha keratinocytes also released KC and MIP-2 into culture supernatants through an NF-kappaB-dependent pathway. MIP-2 and KC mediated the infiltration of neutrophils into the epidermis, since this was prevented by ablating CXCR2 in K5-PKCalpha mice or administering neutralizing antibodies against KC or MIP-2. The neutrophilia resulted from PKCalpha-mediated upregulation of cutaneous G-CSF released into the plasma independent of CXCR2. These responses could be inhibited by topical treatment with a PKCalpha-selective inhibitor. Inhibiting PKCalpha also reduced the basal and TNF-alpha- or TPA-induced expression of CXCL8 in cultured psoriatic keratinocytes, suggesting that PKCalpha activity may contribute to psoriatic inflammation. Thus, skin can be the source of circulating factors that have both local and systemic consequences, and these factors, their receptors, and possibly PKCalpha could be therapeutic targets for inhibition of cutaneous inflammation.

Topics: Adult; Aged; Animals; Antibodies; Chemokine CXCL1; Chemokine CXCL2; Chemokines; Chemokines, CXC; Dermatitis; Epidermis; Female; Gene Expression; Granulocyte Colony-Stimulating Factor; Humans; Interleukin-8; Keratinocytes; Male; Mice; Mice, Knockout; Mice, Transgenic; Middle Aged; Neutrophil Infiltration; Protein Kinase C-alpha; Protein Kinase Inhibitors; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

Omega-3 polyunsaturated fatty acids (n-3 PUFA) inhibit ultraviolet B (UVB)-induced inflammation and other inflammatory states, in vivo. We examined whether this may be mediated by modulation of interleukin (IL)-8, a chemokine pivotal to skin inflammation induced by UVB, in epidermal and dermal cells. We also explored the ability of n-3 PUFA to protect against tumor necrosis factor (TNF)-alpha induction of IL-8, and assessed relative potencies of the principal dietary n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Pre-supplementation, both HaCaT keratinocyte and CCD922SK fibroblast cell lines showed dose-responses for UVB-induced IL-8 release (p<0.001), assessed 48 h post-irradiation. Cells were supplemented with > or =90% purified EPA, DHA, oleic acid (OA) or vehicle control, for 4.5 d. EPA and DHA supplements were bioavailable to keratinocytes and fibroblasts. In keratinocytes, EPA and DHA were shown to reduce basal secretion of IL-8 by 66% and 63%, respectively (p<0.05), and UVB-induced levels by 66% and 65% at 48 h after 100 mJ per cm2, respectively, (p<0.01). A similar pattern occurred in fibroblasts, whereas OA had no influence on IL-8 release in either cell line. In addition, TNF-alpha-induced IL-8 secretion by keratinocytes was reduced by 54% and 42%, respectively, by EPA and DHA (p<0.001). Hence both n-3 PUFA inhibit production of UVB- and TNF-alpha-induced IL-8 in skin cells; this may be important in the photoprotective and other anti-inflammatory effects conferred by these agents.

Topics: Adult; Cell Line, Tumor; Dermatitis; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fibroblasts; Humans; Interleukin-8; Keratinocytes; Male; Melanoma; Middle Aged; Radiation Dosage; Skin Neoplasms; Tumor Necrosis Factor-alpha; Ultraviolet Rays

We describe a non-invasive approach for recovering RNA from the surface of skin via a simple tape stripping procedure that permits a direct quantitative and qualitative assessment of pathologic and physiologic biomarkers. Using semi-quantitative RT-PCR we show that tape-harvested RNA is comparable in quality and utility to RNA recovered by biopsy. It is likely that tape-harvested RNA is derived from epidermal cells residing close to the surface and includes adnexal structures and present data showing that tape and biopsy likely recover different cell populations. We report the successful amplification of tape-harvested RNA for hybridization to DNA microarrays. These experiments showed no significant gene expression level differences between replicate sites on a subject and minimal differences between a male and female subject. We also compared the array generated RNA profiles between normal and 24 h 1% SLS-occluded skin and observed that SLS treatment resulted in statistically significant changes in the expression levels of more than 1,700 genes. These data establish the utility of tape harvesting as a non-invasive method for capturing RNA from human skin and support the hypothesis that tape harvesting is an efficient method for sampling the epidermis and identifying select differentially regulated epidermal biomarkers.

Topics: Actins; Adult; Biopsy; Dermatitis; Female; Humans; Interleukin-1; Interleukin-8; Middle Aged; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Skin; Skin Physiological Phenomena

Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) exerts a potent cytotoxic activity especially against many tumor cell types such as transformed keratinocytes. The specific role of the different TRAIL receptors in this process, however, is unknown. In this report we examine the role the TRAIL receptors play in both the apoptotic and nonapoptotic responses of HaCaT keratinocytes to leucine zipper TRAIL (LZ-TRAIL). By employing receptor-specific blocking antibodies we demonstrate that TRAIL receptor 1 plays the primary role in mediating caspase activation and apoptosis in HaCaT cells. Furthermore, we show that this receptor mainly mediates nuclear factor kappaB activation and expression of the pro-inflammatory cytokine interleukin-8 and that nuclear factor kappaB activation is critically required for the induction of pro-inflammatory cytokines in response to LZ-TRAIL. Taken together, our data suggest that beside its potent pro-apoptotic role, LZ-TRAIL leads to pro-inflammatory responses that are mainly mediated by TRAIL receptor 1 in HaCaT keratinocytes.

Topics: Apoptosis; Apoptosis Regulatory Proteins; Cell Line, Transformed; Chemotaxis; Dermatitis; Gene Expression Regulation; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-8; Keratinocytes; Leucine Zippers; Membrane Glycoproteins; NF-kappa B; Receptors, TNF-Related Apoptosis-Inducing Ligand; Receptors, Tumor Necrosis Factor; Sialoglycoproteins; Signal Transduction; TNF-Related Apoptosis-Inducing Ligand; Transcriptional Activation; Tumor Necrosis Factor-alpha

We have developed a simple noninvasive method to assess inflammatory changes in human skin, even in the absence of visible clinical irritation. Our approach is based on a simple tape (Sebutape) adsorption method to recover molecular mediators of skin inflammation (e.g., cytokines). This procedure has been used to investigate baseline cytokine levels on skin, to assess normal skin condition and to evaluate changes due to chemical insult, existing dermatitis, or sun exposure.. In clinical studies, Sebutape was applied to normal appearing uncompromised skin, as well as to compromised (diaper or heat rash), chemically treated (sodium laurel sulfate), or sun-exposed skin. Sebutape was applied to the skin for a 1 min collection interval. Tapes were extracted in saline using a 10 min sonication, and the extracts were analyzed for human interleukin-1alpha (IL-1alpha), IL-1 receptor antagonist (IL-1RA) and IL-8 using commercial immunoassay test kits. The cytokine levels recovered from each tape extract were normalized to total protein (TP) levels. In infant product use tests, the severity of skin irritation (diaper and heat rash or erythema) was also assessed using a visual grading scale.. The method itself caused minimal, if any, skin damage. Additionally, Sebutape was shown to quantitatively adsorb detectable levels of cytokine from normal-appearing (control) or compromised (e.g., rashed or chemically treated) skin. In infant studies, significant increases in IL-1alpha levels were found in skin exhibiting diaper rash, heat rash and erythema compared with normal appearing control skin sites. When these results were normalized to total protein levels recovered from each tape, the significance was maintained. A positive correlation (r2=0.82) existed between IL-1RA levels and diaper rash severity. Significant increases in IL-8 levels were recovered from diaper rash versus control skin sites. There were differences in baseline cytokine levels in normal skin related to body site and sun exposure. The IL-1 RA/IL-1alpha ratios for sun-exposed skin of the face and lower leg were significantly (P<0.05) higher (3-6-fold) than those for skin sites that typically receive minimal sun exposure (i.e., underarm, upper leg and upper back). There was a significant increase in IL-1alpha and a directional increase in IL-8 levels in adult skin sites treated with the irritant, sodium lauryl sulfate, even in the absence of visible skin irritation (erythema).. Our results demonstrate that this method is a useful noninvasive technique for assessing skin inflammatory events. In addition, the method is simple and easily applied in a clinical setting, whether on infants or adults.

Topics: Adhesives; Adsorption; Aged; Biomarkers; Cytokines; Dermatitis; Environmental Exposure; Forearm; Humans; Infant; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-8; Sialoglycoproteins; Skin; Skin Diseases; Sodium Dodecyl Sulfate; Sunlight; Surface-Active Agents; Time Factors

Peroxisome proliferator-activated receptors (PPAR) are members of a nuclear receptor superfamily, which were initially described in the context of fatty acid degradation and adipocyte differentiation. In this study we tested the hypothesis that peroxisome proliferator-activated receptor activation also controls inflammation. In an in vitro model with human keratinocytes inflammation was mimicked by irradiation with ultraviolet B light (150 mJ per cm(2)). Activators for PPAR-alpha (WY-14,643, clofibrate) were shown to reverse ultraviolet-B-light-mediated expression of inflammatory cytokines (interleukin-6, interleukin-8). An activator preferentially for PPAR-beta (bezafibrate) did not show prominent effects on interleukin-6 and interleukin-8 expression. The anti-inflammatory action of WY-14,643 on skin cells was further demonstrated by in vivo testings in which topically applied WY-14,643 markedly increased the minimal erythema dose in ultraviolet-B-irradiated skin. Additionally, it was shown that ultraviolet B irradiation led to a decrease of all three peroxisome proliferator-activated receptor subsets at the mRNA level. Also transactivation of peroxisome proliferator response element was attenuated by ultraviolet B irradiation. The downregulation of peroxisome proliferator-activated receptors by ultraviolet B irradiation provides a possible mechanism that leads to exaggerated and prolonged inflammation. This work suggests the possibility of PPAR-alpha activators as novel nonsteroidal anti-inflammatory drugs in the topical treatment of common inflammatory skin diseases such as atopic dermatitis, psoriasis, and photodermatitis.

Topics: Cell Division; Cell Line, Transformed; Dermatitis; DNA Primers; Down-Regulation; Erythema; Gene Expression; Humans; Interleukin-6; Interleukin-8; Keratinocytes; Peroxisome Proliferators; Pyrimidines; Receptors, Cytoplasmic and Nuclear; Response Elements; Skin; Transcription Factors; Ultraviolet Rays

To estimate canine interleukin-8 (cIL-8) levels in blood plasma samples, a sandwich enzyme linked immunosorbent assay (ELISA) was established. For the development of the sandwich ELISA, polyclonal anti-cIL-8 (capturing), biotinylated anti-cIL-8 (developing) antibodies and glutathione-S-transferase/cIL-8 (GST/cIL-8) fusion protein as an antigen were used. cIL-8 in the fusion protein of GST/cIL-8 was detected in a dose dependent manner. The lowest limit of GST/cIL-8 detectable by this method was 2 ng/ml of GST/cIL-8 (containing; 0.470 ng/ml of cIL-8). IL-8 levels in the plasma samples from apparently healthy dogs were less than 0.470 ng/ ml. Higher levels of IL-8 were detected in the plasma samples of dogs with cystitis, dermatitis, and gastric cancer. These results suggest that the determination of cIL-8 by the sandwich ELISA is useful in diagnosis of inflammatory diseases in dogs.

Topics: Animals; Biomarkers; Cystitis; Dermatitis; Dog Diseases; Dogs; Enzyme-Linked Immunosorbent Assay; Female; Glutathione Transferase; Indicators and Reagents; Inflammation; Interleukin-8; Male; Orchiectomy; Recombinant Fusion Proteins; Reference Values; Renal Insufficiency; Sensitivity and Specificity; Stomach Neoplasms

The in vivo response to ultraviolet B (UVB) radiation in skin is characterized by the accumulation of both mononuclear and polymorphonuclear cells within the dermis and an induction of vascular endothelial adhesion molecules. Epidermal production of cytokines (IL-8 and TNF-alpha) has been strongly implicated in the development of UVB-induced inflammation. In the current study, we examined the time course of IL-8 and TNF-alpha mRNA and protein expression in the epidermis over a 24-h period after in vivo UVB irradiation. Also, the induction of adhesion molecule expression and the accumulation of neutrophils within the dermis were followed. We found constitutive expression of both cytokines (mRNA and protein) in the epidermis of unirradiated skin. IL-8 was rapidly upregulated after irradiation and mRNA and protein increased at 4 h, reaching a maximum between 8 and 24 h. TNF-alpha mRNA and protein was minimally increased by 8 h after UVB irradiation and reached a maximum by 24 h. No significant alteration in ICAM-1 or VCAM-1 expression was observed. E-selectin expression, which was absent from control samples, was increased from 4 h onward and also reached a maximum at 24 h, coinciding with peak neutrophil accumulation. A strong correlation (r = 0.96) was found between number of E-selectin-positive vessels and numbers of infiltrating neutrophils at this time. Moreover, because E-selectin expression was increased before any apparent increase in TNF-alpha protein (4 h), TNF-alpha does not appear to be involved in the early induction of the adhesion molecule, but cytokines such as TNF-alpha and IL-8 may act subsequently to augment the inflammatory response.

Topics: Adult; Dermatitis; E-Selectin; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Leukocyte Count; Male; Microcirculation; Neutrophils; Skin; Tumor Necrosis Factor-alpha; Ultraviolet Rays; Up-Regulation; Vascular Cell Adhesion Molecule-1

Topics: Amino Acid Sequence; Biological Assay; Cell Degranulation; Chemokine CCL5; Chemokine CXCL1; Chemokines; Chemokines, CC; Chemokines, CXC; Chemotactic Factors; Chemotaxis, Leukocyte; Chromatography, Gel; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Dermatitis; Electrophoresis, Polyacrylamide Gel; Glucuronidase; Growth Substances; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Leukocytes; Molecular Sequence Data; Peptide Fragments; Psoriasis; Skin

Psoriasis is a common chronic skin disease mediated by cellular immune mechanisms and characterized by an intense neutrophil cell infiltrate and proliferative activation of epidermal keratinocytes. We have previously described the expression of the inducible nitric oxide synthase (iNOS) in epidermal keratinocytes of psoriatic skin lesions. In this study, the role of iNOS in psoriatic inflammation was explored ex vivo in psoriatic skin biopsies and in vitro in primary cultures of human keratinocytes. Messenger RNA for the iNOS enzyme (iNOS mRNA) was detected by reverse transcriptase polymerase chain reaction in skin biopsies from patients with psoriasis, but not in skin specimens from patients with atopic eczema or from healthy volunteers. As demonstrated by in situ hybridization and immunohistochemistry, expression of iNOS mRNA and its gene product was localized to the epidermal keratinocytes of psoriatic skin lesions. In situ hybridization further revealed a complete colocalization of mRNA expression for iNOS with interleukin (IL) 8 receptor-specific mRNA either in the basal germinative cell layer or at focal sites of ongoing neutrophil inflammation in suprabasal cell layers. Because psoriatic keratinocytes have previously been shown to express mRNA transcripts for IL-8, it seemed reasonable to hypothesize that iNOS expression could be induced in an autocrine loop by IL-8. This hypothesis was substantiated by our in vitro experiments showing that a combination of IL-8 and interferon gamma induces the expression of iNOS-specific mRNA and of the functional enzyme in cultured human keratinocytes. These results suggest an important role for iNOS in concert with IL-8 and its receptor early during the formation of psoriatic lesions.

Topics: Biopsy; Cells, Cultured; Dermatitis; Humans; Immunohistochemistry; In Situ Hybridization; Interleukin-8; Keratinocytes; Nitric Oxide Synthase; Polymerase Chain Reaction; Psoriasis; RNA, Messenger

Topics: Cells, Cultured; Chemotactic Factors; Cytokines; Dermatitis; Humans; Interleukin-1; Interleukin-8; Monocyte Chemoattractant Proteins; Psoriasis; RNA; Skin; Tumor Necrosis Factor-alpha

Ovine IL-8 (oIL-8) cDNA was obtained by probing a spleen cell cDNA library with human IL-8 (hIL-8) cDNA. The oIL-8 cDNA was 1434 base pairs long with a single open reading frame encoding a 101 amino acid precursor protein of relative molecular mass 11,268. The inferred amino acid sequence has 78, 82, 84 and 67% similarity with human, rabbit, porcine and guinea-pig IL-8, respectively. By analogy with the most prevalent form of hIL-8, a 72 amino acid form of oIL-8 was expressed as a fusion protein containing glutathione-S-transferase and purified by affinity chromatography on a glutathione-Sepharose column yielding 8 mg IL-8/L broth culture. The fusion protein lacked chemotactic activity for ovine neutrophils, whereas the 72 amino acid form of oIL-8 was equipotent with rhIL-8. At 6 and 24 h after intradermal injection of 10(-9) mol oIL-8, there was intense accumulation of neutrophils, and very mild accumulation of eosinophils, CD5, CD4 and T19 (a gamma delta TCR subset) cells but not CD8 cells. The availability of roIL-8 and its cDNA probes will permit the role of this important member of the IL-8 family of chemotactic cytokines to be determined in inflammatory diseases of sheep.

Topics: Amino Acid Sequence; Animals; Base Sequence; Chemotaxis, Leukocyte; Cloning, Molecular; Dermatitis; DNA; Eosinophils; Gene Expression Regulation; Interleukin-8; Leukocyte Count; Male; Molecular Sequence Data; Neutrophils; Recombinant Fusion Proteins; Sequence Homology, Amino Acid; Sheep; Sheep Diseases; Skin

ETH615 (4-[2-quinolylmethoxy]-N-[3-fluorobenzyl]-phenylaminometh yl-4-benzoic acid) is a potent inhibitor of leukotriene biosynthesis in A23187-stimulated leukocytes, and of IL-8 gene expression in LPS-stimulated PBMC. It shows anti-inflammatory activity in a canine model of dermal inflammation. A topical formulation is present in phase II clinical trials. In the present study the effect of ETH615 on oxazolone-induced acute inflammation and phorbol ester-induced chronic inflammation in the mouse ear was investigated. Betamethasone (0.04 mg/ear) and ETH615 (1-1.5 mg/ear) significantly inhibited both the oedema formation and the PMN infiltration. The cream and ointment formulations of ETH615 developed for clinical studies were equally active. ETH615 is thus an anti-inflammatory agent in these murine models of dermatosis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Betamethasone; Dermatitis; Disease Models, Animal; Ear; Edema; Gene Expression; Interleukin-8; Leukotriene B4; Mice; Oxazolone; Peroxidase; Quinolines; T-Lymphocytes; Tetradecanoylphorbol Acetate

In order to establish the pathophysiological roles of IL-8, rabbit IL-8 was expressed in Escherichia coli and purified to homogeneity by sequential chromatography on heparin agarose, CM-HPLC, and RP-HPLC. The purified recombinant rabbit IL-8 was homogeneous on SDS-PAGE and the ED50 of neutrophil chemotactic activity for rabbit peritoneal neutrophils was 2 ng/ml. The binding of 125I-labeled rabbit IL-8 to rabbit neutrophils was inhibited by unlabeled human IL-8 as well as rabbit IL-8 but not by another leucocyte chemotactic cytokine (chemokine), monocyte chemotactic and activating factor. Scatchard plot analysis of the binding of 125I-labeled rabbit IL-8 to rabbit peritoneal neutrophils revealed that the rabbit neutrophils have two affinity classes of receptors for IL-8 (Kd = 2.3 nM, 4.1 x 10(4) sites/cell; Kd = 18.0 nM, 11.4 x 10(4) sites/cell). It was found that a previously generated mouse anti-human IL-8 mAb, WS-4, inhibited the binding of 125I-labeled rabbit IL-8 to rabbit neutrophils, and blocked neutrophil chemotaxis in vitro in a specific and dose-dependent manner. An ELISA system for rabbit IL-8 was established using this mAb and guinea pig polyclonal antibodies to recombinant rabbit IL-8 to measure the levels of IL-8 in rabbit plasma. Intravenous administration of lipopolysaccharide (LPS) (100 micrograms) in rabbits caused the highest level of IL-8 in blood at around 2 h. Intravenous administration of WS-4 (10 mg) inhibited neutrophil infiltration at the site of LPS injection into the rabbit skin, suggesting that IL-8 is essential in the recruitment of neutrophils at sites of acute inflammation in vivo.

Topics: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Base Sequence; Chemotaxis, Leukocyte; Cloning, Molecular; Cross Reactions; Dermatitis; DNA; Escherichia coli; Female; Gene Expression; Humans; Interleukin-8; Lipopolysaccharides; Molecular Sequence Data; Neutrophils; Rabbits; Recombinant Proteins

1. The intradermal administration of endothelial IL-8 (IL-8(1-77) or monocyte derived IL-8 (IL-8(1-72) to rabbits produced a concentration-dependent increase in plasma extravasation and an accumulation of polymorphonuclear leukocytes (PMNs) when measured over a 3 h time period. When plasma extravasation and PMN accumulation were measured over a 30 min time period no significant increases in PMN accumulation or plasma extravasation were observed in response to IL-8 alone. However, under these conditions, the addition of prostaglandin E2 (100 pmol) produced a significant potentiation of IL-8-induced plasma extravasation. There was no significant difference between the biological activities of IL-8(1-77) and IL-8(1-72). 2. Plasma extravasation and PMN accumulation induced by IL-8 were inhibited in rabbits pretreated with the monoclonal antibody designated IB4 (1 mg kg-1, i.v.) directed against the common beta chain (CD18) of the leukocyte integrins. 3. The intra-articular administration to rabbits of IL-8(1-77) (1 nmol) resulted 24 h later in the appearance of a mixed population of leukocytes (PMNs and mononuclear cells) in synovial lavage fluid. Biochemical analyses revealed the presence of an increased level of sulphated proteoglycans (sPG) and of the metalloproteinase stromelysin. Pretreatment of rabbits with IB4 (3 mg kg-1, i.v.) inhibited the accumulation of PMNs but had no effect on the mononuclear infiltrate nor on the levels of sPG or stromelysin. 4. The intradermal or intra-articular injection of E. coli-derived endotoxin induced similar inflammatory changes to those observed with IL-8.The possibility that the biological activities of IL-8 were attributable to minor contamination with endotoxin is unlikely for two reasons. Firstly, biological effects of endotoxin were observed at levels greater than that contained in the IL-8 preparation. Secondly,reduction of the endotoxin content of the IL-8 preparation by a factor of 10 did not produce a concomitant reduction in the observed biological activity of the IL-8.

Topics: Animals; Antibodies, Monoclonal; Antigens, CD; CD18 Antigens; Dermatitis; Endotoxins; Escherichia coli; Female; Interleukin-8; Matrix Metalloproteinase 3; Metalloendopeptidases; Neutrophils; Proteoglycans; Rabbits; Synovial Fluid; Synovitis; Therapeutic Irrigation

T lymphocytes and mononuclear cells preferentially accumulate in the epidermis in inflammatory skin disease. To determine the role of keratinocytes in both the chemotaxis and adhesion of these cells to the epidermis, cultured keratinocytes were incubated with IFN-gamma and tumor necrosis factor-alpha (TNF-alpha), and mRNA detected and quantitated for IL-8, monocyte chemotaxis and activating factor, and intercellular adhesion molecule-1. Whereas induction of these mRNAs was either absent, or relatively weak and transient, to either IFN-gamma or TNF-alpha alone, when administered in combination there was a dramatic increase and persistence in the induction of all three genes. Pretreatment of the keratinocytes with cycloheximide failed to eliminate transcription, implying that all three are primary response genes. Transforming growth factor-beta, which modulates other keratinocyte functions (not related to adhesion or chemotaxis of inflammatory cells) failed to induce any of the genes. These novel findings potentially explain the selective recruitment of T cells and monocytes observed in inflammatory skin disease, because IFN-gamma and TNF-alpha can co-ordinately regulate keratinocyte-derived chemoattractants and adhesion molecule production.

Topics: Cell Adhesion Molecules; Cells, Cultured; Chemotactic Factors; Dermatitis; Humans; Interferon-gamma; Interleukin-8; Interleukins; Keratinocytes; RNA, Messenger; T-Lymphocytes; Tumor Necrosis Factor-alpha

The mode of extravasation of neutrophils (PMNs) in cutaneous inflammation was studied in sequential biopsy specimens taken from human skin. Inflammatory skin reactions were produced by intracutaneous injection of endogeneous mediators of inflammation--C5ades arg, LTB4, neutrophil-activating peptide (NAP) and interleukin-1 (IL-1). Within 30 min after injection neutrophils were observed in close contact with endothelial cells of postcapillary venules and, following cytoplasmic engulfment, the cells were found to be transported transcellulary through the endothelial layer. In a total of 20 biopsy specimens taken at various times, cell migration via interendothelial gaps was absent. Instead, the transcellular pathway appeared to be the first and foremost mode of diapedesis. During this migratory process PMNs lacked signs of degranulation and numerous electron-lucent vesicles and secondary lysosomes were found. In addition, coated pits present on leukocyte as well as endothelial-cell membranes were indicative of receptor-mediated endocytotic processes.

Topics: Cell Movement; Complement C5a, des-Arginine; Dermatitis; Endothelium, Vascular; Humans; Interleukin-1; Interleukin-8; Leukotriene B4; Neutrophils; Peptides; Skin