lewis-x-antigen and Psoriasis

IL-9 is present in psoriatic lesions and is produced by lymphocytes. However, it is not known whether this cytokine is induced by relevant pathogenic triggers of psoriasis, such as Streptococcus pyogenes. Here we addressed the production of IL-9 in response to various pathogens in a psoriatic ex vivo model. Extracts of S. pyogenes and Candida albicans triggered the production of IL-9 and also IL-17A and IFN-γ. This induction was dependent on the interaction between CLA

Topics: HLA Antigens; Humans; Interferon-gamma; Interleukin-17; Interleukin-9; Lewis X Antigen; Oligosaccharides; Psoriasis; Severity of Illness Index; Sialyl Lewis X Antigen; Streptococcus pyogenes; T-Lymphocytes

The biologically active vitamin D analog calcipotriol is effective and safe in the topical treatment of psoriasis, but its exact mechanism of action is unknown.. We investigated expression of 1,25-dihydroxyvitamin D3 receptors, markers for inflammation (CD1a, CD4, CD8, CD11b, CD15; NAP-1/interleukin-8; 55 kd tumor necrosis factor-receptor; intercellular adhesion molecule-1; HLA-DR), proliferation (proliferating cell nuclear antigen, Ki-67), and differentiation (transglutaminase K; involucrin; cytokeratin 16) in psoriatic skin during topical calcipotriol treatment.. For immunohistochemical staining we used the labeled avidin-biotin technique on cryostat-cut sections.. We found a significant increase of 1,25-dihydroxyvitamin D3 receptor expression in epidermal basal keratinocytes of lesional psoriatic skin during calcipotriol treatment. In all patients analyzed, effects on proliferation and differentiation of epidermal keratinocytes were stronger than effects on dermal inflammation. Effects on inflammation were more pronounced in the epidermal than in the dermal compartment.. Our findings indicate that analogs of 1,25-dihydroxyvitamin D3 upregulate their corresponding receptor in human keratinocytes in vivo. This mechanism may be important in the therapeutic efficacy of vitamin D analogs in psoriasis. The differential therapeutic effects in the epidermal and dermal skin compartments may be due to a reduced bioavailability of calcipotriol in the dermal compartment.

Topics: Administration, Cutaneous; Antigens, CD; Antigens, CD1; Biological Availability; Calcitriol; CD11 Antigens; CD4 Antigens; CD8 Antigens; Cell Differentiation; Cell Division; Dermatologic Agents; Epidermis; Gene Expression Regulation; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Immunohistochemistry; Intercellular Adhesion Molecule-1; Interleukin-8; Keratinocytes; Keratins; Lewis X Antigen; Male; Proliferating Cell Nuclear Antigen; Protein Precursors; Psoriasis; Receptors, Calcitriol; Receptors, Interleukin; Receptors, Interleukin-8A; Receptors, Tumor Necrosis Factor; Skin; Transglutaminases; Tumor Necrosis Factor-alpha; Up-Regulation

The roles of sialyl-Lewisx antigen were evaluated in the pathogenesis of psoriasis. Sialyl-Lewisx expression was investigated immunohistochemically in the epidermis of normal human skin and erythematous lesional skin of psoriasis vulgaris by avidin-biotin-peroxidase complex procedures. A few sialyl-Lewisx positive dendritic cells were detected in the epidermis of normal human skin. In 7 out of 9 cases of psoriasis vulgaris, the number of sialyl-Lewisx-positive epidermal dendritic cells increased in the erythematous lesion over the adjacent normal skin; there were no marked changes in the numbers of CD1a-positive cells in the epidermis between the two skin types. In the double immunofluorescence studies, more than half of the sialyl-Lewisx-positive epidermal cells in psoriatic erythema were stained with a monoclonal Lag antibody that specifically reacts with Birbeck granules and related structures of human Langerhans cells. Furthermore, we determined the changes in serum levels of sialyl-Lewisx antigens in patients with psoriasis. Although levels in the sera were not significantly elevated over those of controls, the increases correlated with the degree of disease activity. These findings suggest that sialyl-Lewisx antigen is possibly involved in the development of psoriasis.

Topics: Biopsy, Needle; Case-Control Studies; Female; Humans; Immunohistochemistry; Langerhans Cells; Lewis X Antigen; Male; Psoriasis; Skin

Cellular adhesion molecules play a central role in leucocyte migration through peripheral blood and tissues. A crucial stage in these events in selectin-mediated adhesion involving E-selectin expressed on activated endothelium interacting with a range of carbohydrate ligands expressed by specific subpopulations of leucocytes. As such mechanisms may be relevant to bone marrow-derived dendritic epidermal Langerhans' cell (LC) migration, expression of these carbohydrate ligands was assessed immunocytochemically in whole skin biopsies and in epidermal cell suspensions obtained from adult humans. Double-labelling experiments revealed that sialyl Lewis x, recognized by the monoclonal antibody CSLEX1, was expressed on epidermal LC (n = 9). Furthermore, expression was enhanced at 24 hr following epicutaneous application of antigen and in the inflammatory disorder psoriasis (n = 10). E-selectin was concomitantly strongly expressed on dermal endothelium in psoriasis and allergic contact dermatitis. Intradermal injection of the T-cell-derived cytokine interferon-gamma (IFN-gamma) led to increased LC expression of sialyl Lewis x. In epidermal cell suspensions, in contrast to keratinocytes, CD1a+ cells expressed sialyl Lewis x, intensity of which was enhanced after 4 days in culture. CSLEX1 staining could be abolished and CD15 (non-sialated Lewis x) expression induced by saponification and treatment with neuraminidase. Expression of other selectin ligands was also examined. While the cutaneous lymphocyte antigen defined by the monoclonal antibody HECA-452 reacted with a small minority of LC, sialyl Lewis a and sulphatide were not expressed under any experimental conditions. These studies indicate that E-selectin-sialyl Lewis x interactions are potentially important in LC migration, both into and out of skin.

Topics: Adult; Antigens, CD; Antigens, CD1; Antigens, Differentiation, Myelomonocytic; Dermatitis, Allergic Contact; Epidermis; Humans; Immunoenzyme Techniques; Interferon-gamma; Langerhans Cells; Lewis X Antigen; Ligands; Neuraminidase; Oligosaccharides; Psoriasis; Recombinant Proteins; Sialyl Lewis X Antigen; Skin

A histological-immunohistological study was conducted to investigate the effect of systemically administered fumaric acid esters (FAEs) on epidermal thickness and composition of the inflammatory infiltrate in psoriatic plaques. The very first effect of systemic therapy with FAEs is the disappearance of CD 15-positive cells in the beneath the epidermis, accompanied by a significant reduction in T-helper cells beneath the epidermis, pointing to an immunosuppressive effect. This is followed after some delay by a reduction in acanthosis and hyperkeratosis. The reduction in infiltrating T-lymphocytes corresponds to that seen after systemic or intralesional therapy with cyclosporin. However, the normalization of the psoriatic plaques takes longer under the influence of FAEs than under cyclosporin.

Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Esters; Female; Fumarates; Humans; Lewis X Antigen; Lymphocyte Subsets; Male; Middle Aged; Psoriasis; Skin

The results of several investigations proved that, in special circumstances, human keratinocytes (HKs) synthesize and express cell surface moieties characteristic of effector and/or accessory cells of the immune system, such as CD16, CD36, HLA-DR, and intercellular adhesion molecule-1 (CD54), which are all detectable on the surfaces of macrophages. In the present study, skin biopsies from healthy volunteers, from positive tuberculin skin tests, and from patients with acute urticaria (AU), lichen planus (LP), psoriasis vulgaris (PV), mycosis fungoides (MF), and purpura pigmentosa chronica (PPC) were investigated by means of a multistep immunoperoxidase method to examine the reactivity of the HKs with a panel of monoclonal antibodies (MABs) characteristic of monocyte/macrophage cell lines. In biopsies obtained from positive tuberculin tests and from clinically involved skin of patients with LP, PV, MF, or PPC, a multifocal, positive peroxidase reaction was observed on the membranes of HKs of the basal and suprabasal cell layers when the MABs OKM13 (CD13), OKM14 (CD14), and Dako-Macrophage (CD68) were used. In contrast, specific staining of the HKs was not observed with the same antibodies in the biopsies of healthy volunteers or of patients with AU or in the uninvolved skin specimens obtained from the other patients. The HKs of PV, LP, MF, PPC, and AU patients and those of the healthy subjects all failed to give positive reactions when MABs against CD11b, CD15, or CD33 were used. The published data supplement the known surface characteristics of HKs, reflecting their stage of activation and differentiation.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antigens, Surface; Biomarkers, Tumor; CD13 Antigens; Humans; Immunohistochemistry; Keratinocytes; Lewis X Antigen; Lichen Planus; Lipopolysaccharide Receptors; Macrophage-1 Antigen; Membrane Glycoproteins; Monocytes; Mycosis Fungoides; Psoriasis; Purpura; Sialic Acid Binding Ig-like Lectin 3; Skin; Skin Diseases; Skin Neoplasms; Tuberculosis, Cutaneous; Urticaria