leukotriene-b4 and Eosinophilia

Topics: Animals; Asthma; Cysteine; Eosinophilia; Humans; Leukotriene B4; Leukotrienes; Neutrophils

The role of exhaled H2S as a marker of airway inflammation and its relationship with COPD severity remain to be determined.. Airway inflammation was classified in 77 COPD subjects based on the presence of inflammatory cells in induced sputum. We investigated the association between disease phenotype and exhaled H2S, lung function, and plasma levels of several inflammatory factors, including tumor necrosis factor alpha, interleukin-8, and leukotriene B4.. In total, 33.77% of enrolled COPD subjects were diagnosed with eosinophilia. These subjects had a longer disease course, smoked fewer cigarettes, and experienced more frequent exacerbation events before study enrollment. However, they also had worse lung function and larger residual volume, they demonstrated greater changes in FEV1 following bronchodilator inhalation. Although levels of plasma inflammatory factors did not significantly differ between subjects with and without eosinophilia, subjects without eosinophilia had significantly higher levels of exhaled H2S (9.19±2.74 vs 7.24±1.68 parts per billion, P=.01). Furthermore, exhaled H2S levels were negatively correlated with induced sputum eosinophils (r=-0.45, P=.05), and positively correlated with inspiratory capacity in COPD subjects (r=0.51, P=.026), but did not correlate significantly with plasma inflammatory factors. A cut-off value of 7.10 parts per billion of exhaled H2S predicted a non-eosinophilic phenotype with 68.6% sensitivity and 77.9% specificity.. Exhaled levels of H2S were lower in subjects with eosinophilia. Increased levels of exhaled H2S predicted a non-eosinophilic phenotype in our study population.

Topics: Aged; Area Under Curve; Biomarkers; Breath Tests; Eosinophilia; Eosinophils; Exhalation; Female; Forced Expiratory Volume; Humans; Hydrogen Sulfide; Inflammation; Inspiratory Capacity; Interleukin-8; Leukotriene B4; Male; Middle Aged; Phenotype; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; Residual Volume; ROC Curve; Sputum; Tumor Necrosis Factor-alpha

Leukotriene B4 (LTB4) has been implicated in the pathogenesis of allergic diseases. BLT2, a low-affinity LTB4 receptor, is activated by LTB4 and 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT). Although the high-affinity LTB4 receptor BLT1 has been shown to exert proinflammatory roles, the role of BLT2 in allergic inflammation has not been clarified. To study the function of BLT2 in development of asthma, we used mice model of ovalbumin (OVA)-induced allergic airway disease. The 12-HHT levels were elevated in bronchoalveolar lavage (BAL) fluids of OVA-sensitized/challenged wild-type mice. BLT2-deficient mice exhibited enhanced eosinophilia in BAL fluids after OVA exposure. Interleukin (IL)-13 levels in BAL fluids and IL-13-producing CD4(+) T cells in the lungs were elevated in BLT2-deficient mice compared to wild-type mice, whereas the levels of IL-4, IL-5, and interferon (IFN)-γ in BAL fluids and serum OVA-specific IgE were comparable. Transfection of BLT2-specific small interfering RNA enhanced IL-13 production in CD4(+) T cells in vitro. Expression of BLT2 mRNA in CD4(+) T cells was significantly reduced in patients with asthma compared to healthy control subjects. These findings indicate that BLT2 has a protective role in allergic airway inflammation and that diminished BLT2 expression in CD4(+) T cells may contribute to the pathophysiology of asthma.

Topics: Adult; Aged; Animals; Asthma; Bronchoalveolar Lavage Fluid; Calcium; CD4-Positive T-Lymphocytes; CHO Cells; Cricetinae; Cricetulus; Cytokines; Eosinophilia; Fatty Acids, Unsaturated; Humans; Leukotriene B4; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Receptors, Leukotriene B4; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Young Adult

D prostanoid receptor 2 (DP₂) [also known as chemoattractant receptor-homologous molecule expressed on T helper 2 (Th2) cells (CRTH2)] is selectively expressed by Th2 lymphocytes, eosinophils, and basophils and mediates recruitment and activation of these cell types in response to prostaglandin D₂ (PGD₂). (5-Fluoro-2-methyl-3-quinolin-2-ylmethylindo-1-yl)-acetic acid (OC000459) is an indole-acetic acid derivative that potently displaces [³H]PGD₂ from human recombinant DP₂ (K(i) = 0.013 μM), rat recombinant DP₂ (K(i) = 0.003 μM), and human native DP₂ (Th2 cell membranes; K(i) = 0.004 μM) but does not interfere with the ligand binding properties or functional activities of other prostanoid receptors (prostaglandin E₁₋₄ receptors, D prostanoid receptor 1, thromboxane receptor, prostacyclin receptor, and prostaglandin F receptor). OC000459 inhibited chemotaxis (IC₅₀ = 0.028 μM) of human Th2 lymphocytes and cytokine production (IC₅₀ = 0.019 μM) by human Th2 lymphocytes. OC000459 competitively antagonized eosinophil shape change responses induced by PGD₂ in both isolated human leukocytes (pK(B) = 7.9) and human whole blood (pK(B) = 7.5) but did not inhibit responses to eotaxin, 5-oxo-eicosatetraenoic acid, or complement component C5a. OC000459 also inhibited the activation of Th2 cells and eosinophils in response to supernatants from IgE/anti-IgE-activated human mast cells. OC000459 had no significant inhibitory activity on a battery of 69 receptors and 19 enzymes including cyclooxygenase 1 (COX1) and COX2. OC000459 was found to be orally bioavailable in rats and effective in inhibiting blood eosinophilia induced by 13,14-dihydro-15-keto-PGD₂ (DK-PGD₂) in this species (ED₅₀ = 0.04 mg/kg p.o.) and airway eosinophilia in response to an aerosol of DK-PGD₂ in guinea pigs (ED₅₀ = 0.01 mg/kg p.o.). These data indicate that OC000459 is a potent, selective, and orally active DP₂ antagonist that retains activity in human whole blood and inhibits mast cell-dependent activation of both human Th2 lymphocytes and eosinophils.

Topics: Animals; Apoptosis; Arachidonic Acids; Binding, Competitive; Calcium Signaling; Cell Membrane; Cell Shape; Chemokine CCL11; Chemotaxis; CHO Cells; Complement C5a; Cricetinae; Culture Media, Conditioned; Eosinophilia; Eosinophils; Guinea Pigs; Humans; Indoleacetic Acids; Interleukin-13; Interleukin-5; Leukotriene B4; Lymphocyte Activation; Mast Cells; Prostaglandin Antagonists; Prostaglandin D2; Pulmonary Eosinophilia; Quinolines; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Immunologic; Receptors, Prostaglandin; Recombinant Proteins; Th2 Cells; Transfection

It is well known that eosinophilia is a key pathogenetic component of toxocariasis. The objective of the present study was to determine if there is an association between peritoneal and blood eosinophil influx, mast cell hyperplasia and leukotriene B(4) (LTB(4)) production after Toxocara canis infection. Oral inoculation of 56-day-old Wistar rats (N = 5-7 per group) with 1000 embryonated eggs containing third-stage (L3) T. canis larvae led to a robust accumulation of total leukocytes in blood beginning on day 3 and peaking on day 18, mainly characterized by eosinophils and accompanied by higher serum LTB(4) levels. At that time, we also noted increased eosinophil numbers in the peritoneal cavity. In addition, we observed increased peritoneal mast cell number in the peritoneal cavity, which correlated with the time course of eosinophilia during toxocariasis. We also demonstrated that mast cell hyperplasia in the intestines and lungs began soon after the T. canis larvae migrated to these compartments, reaching maximal levels on day 24, which correlated with the complete elimination of the parasite. Therefore, mast cells appear to be involved in peritoneal and blood eosinophil infiltration through an LTB(4)-dependent mechanism following T. canis infection in rats. Our data also demonstrate a tight association between larval migratory stages and intestinal and pulmonary mast cell hyperplasia in the toxocariasis model.

Topics: Animals; Eosinophilia; Hyperplasia; Intestines; Leukotriene B4; Lung; Male; Mast Cells; Peritoneal Cavity; Rats; Rats, Wistar; Toxocara canis; Toxocariasis

A very low dose of dexamethasone (DEX) was as equally as sufficient as a pharmacological dose to decrease eosinophil inflammation in airways and bone marrow. The timing of DEX treatment in relation to allergen challenge was strongly decisive for the outcome of the inflammatory response.. We aimed to study compartmental allergic airway inflammatory responses to classic pharmacological and also extremely low physiological DEX dosage, given at different time points close to allergen challenge in a murine model.. Ovalbumin-sensitized BALB/c-mice were exposed to intra-nasal ovalbumin. DEX was given i.p. as 1 microg/kg low-dose or 500 microg/kg pharmacological single-dose 2 h before, immediately before or 7 h after each of three challenges. Inflammatory cells were evaluated in bronchoalveolar lavage (BAL), lungs, nasal mucosa, and bone marrow.. Groups treated with low-dose DEX decreased eosinophilia in BAL to the same extent as the pharmacological dose, but only when administered before challenge. The most prominent decrease of eosinophils in BAL was seen in mice treated with the low dose 2 h before challenge. A similar response pattern as in BAL eosinophilia was detected in lung histopathology. DEX treatments had no obvious effects on inflammation in nasal mucosa.

Topics: Animals; Anti-Inflammatory Agents; Bone Marrow; Bronchoalveolar Lavage Fluid; Dexamethasone; Dose-Response Relationship, Drug; Eosinophilia; Eosinophils; Injections, Intraperitoneal; Leukocyte Count; Leukotriene B4; Lung; Male; Mice; Mice, Inbred BALB C; Nasal Mucosa; Ovalbumin; Premedication; Pulmonary Eosinophilia; Respiratory Hypersensitivity

Statins have been proposed as a novel treatment of respiratory diseases. To determine the beneficial effects of statins on allergic bronchial asthma, the effect of systemic treatment with lovastatin on antigen-induced airway inflammation was investigated.. Male BALB/c mice were used.. Mice were sensitized and repeatedly challenged with ovalbumin (OA) antigen to induce asthmatic response. Animals were also treated with lovastatin (4 mg/kg/day, i.p.) once a day prior to and during the antigen inhalation period.. Inflammatory cell counts and levels of interleukin (IL)-4, IL-13, eotaxin, thymus and activation-regulated chemokine and leukotriene B(4) (LTB(4)) in bronchoalveolar lavage (BAL) fluids were measured.. Significant increases in eosinophils and levels of the T helper 2 cytokines, chemokines and LTB(4) in BAL fluids in association with the increments of total and OA-specific immunoglobulin E (IgE) in sera were observed in the repeatedly antigen-challenged mice. The airway eosinophilia was ameliorated by lovastatin, whereas it had no significant effect on the levels of these inflammatory mediators or IgE.. Lovastatin may be beneficial for the treatment of allergic inflammatory diseases in the airways, such as allergic bronchial asthma.

Topics: Animals; Anti-Inflammatory Agents; Antigens; Asthma; Bronchoalveolar Lavage Fluid; Cell Count; Cytokines; Disease Models, Animal; Eosinophilia; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunoglobulin E; Inflammation Mediators; Leukotriene B4; Lovastatin; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Pneumonia

Subcutaneous heat-coagulated egg white implants (EWI) induce chronic, intense local eosinophilia in mice, followed by asthma-like responses to airway ovalbumin challenge. Our goal was to define the mechanisms of selective eosinophil accumulation in the EWI model. EWI carriers were challenged i.p. with ovalbumin and the contributions of cellular immunity and inflammatory mediators to the resulting leukocyte accumulation were defined through cell transfer and pharmacological inhibition protocols. Eosinophil recruitment required Major Histocompatibility Complex Class II expression, and was abolished by the leukotriene B4 (LTB4) receptor antagonist CP 105.696, the 5-lipoxygenase inhibitor BWA4C and the 5-lipoxygenase activating protein inhibitor MK886. Eosinophil recruitment in EWI carriers followed transfer of: a) CD4+ (but not CD4-) cells, harvested from EWI donors and restimulated ex vivo; b) their cell-free supernatants, containing LTB4. Restimulation in the presence of MK886 was ineffective. CC chemokine receptor ligand (CCL)5 and CCL2 were induced by ovalbumin challenge in vivo. mRNA for CCL17 and CCL11 was induced in ovalbumin-restimulated CD4+ cells ex vivo. MK886 blocked induction of CCL17. Pretreatment of EWI carriers with MK886 eliminated the effectiveness of exogenously administered CCL11, CCL2 and CCL5. In conclusion, chemokine-producing, ovalbumin-restimulated CD4+ cells initiate eosinophil recruitment which is strictly dependent on LTB4 production.

Topics: Allergens; Animals; CD4-Positive T-Lymphocytes; Cell Movement; Chemokines; Chronic Disease; Dexamethasone; Eosinophilia; Eosinophils; Indoles; Inflammation; Leukotriene B4; Male; Mice; Mice, Inbred BALB C; Ovalbumin

Cough is a common symptom in idiopathic pulmonary fibrosis that is difficult to treat and has a major impact on quality of life. We tested the hypothesis that the cough and increased cough reflex sensitivity seen in patients with idiopathic pulmonary fibrosis may be due to airway inflammation in a prospective, cross-sectional study.. We measured the induced sputum inflammatory cell profile and cell-free supernatant inflammatory mediator concentrations in 15 patients with idiopathic pulmonary fibrosis, 17 healthy controls and 15 patients with chronic obstructive pulmonary disease.. Both the geometric mean sputum differential eosinophil cell count and median eosinophilic-cationic-protein concentration were significantly higher in patients with idiopathic pulmonary fibrosis than controls (2.1% vs 0.3%; p <0.001 and 1.1 mg/ml versus 0.2 mg/ml; p=0.03 respectively). There were no significant differences in sputum eosinophil counts and eosinophilic-cationic-protein concentrations between patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease. Sputum leukotriene-B4 concentrations were significantly lower in patients with idiopathic pulmonary fibrosis (p=0.03) and chronic obstructive pulmonary disease (p=0.008) compared to controls.. Idiopathic pulmonary fibrosis is characterised by the presence of active eosinophilic airway inflammation raising the possibility that airway inflammation may contribute to symptoms such as cough.

Topics: Aged; Case-Control Studies; Cross-Sectional Studies; Eosinophil Cationic Protein; Eosinophilia; Eosinophils; Female; Humans; Leukocyte Count; Leukotriene B4; Male; Middle Aged; Osmolar Concentration; Pneumonia; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Spirometry; Sputum

Eosinophils are important inflammatory cells in allergic diseases. Recent evidence suggests that priming mechanisms in the blood may be important for effective eosinophil recruitment to sites of allergic inflammation. We have investigated whether priming an inflammatory site could enhance eosinophil recruitment in vivo. Pretreatment of skin sites in the guinea pig with a low dose (30 ng) of LPS, which had little effect on eosinophil accumulation alone, enhanced by up to threefold the 111In-eosinophil accumulation in response to a passive cutaneous anaphylactic reaction and to intradermally injected eosinophil chemoattractants (leukotriene B4, PAF, and C5ades Arg). In contrast, LPS pretreatment did not enhance accumulation of 111In-neutrophils. Priming was seen only with a 1-h pretreatment time and was not associated with an increase in local edema or a change in cutaneous blood flow. It was independent of local protein synthesis, as assessed using cycloheximide, and was unaffected by a PAF antagonist, a 5-lipoxygenase inhibitor, and the IL-1 receptor antagonist. The priming response was, however, reduced by co-injection with the LPS of TNFR-IgG, but not of CD4-IgG. Blockade of CD18 showed this adhesion molecule to be critical for eosinophil accumulation, and LPS-primed sites were inhibited as effectively as nonprimed sites. In conclusion, low dose LPS pretreatment of guinea pig skin sites primes for eosinophil accumulation induced by intradermally injected inflammatory mediators and cutaneous anaphylactic reaction. This may be an important process by which eosinophil recruitment is modulated in vivo.

Topics: Animals; Antibodies, Monoclonal; Antigens, CD; Azepines; CD18 Antigens; Chemotactic Factors, Eosinophil; Chemotaxis, Leukocyte; Complement C5a, des-Arginine; Cycloheximide; Drug Synergism; Edema; Eosinophilia; Eosinophils; Female; Guinea Pigs; Immunoglobulin G; Interleukin 1 Receptor Antagonist Protein; Leukocyte Count; Leukotriene B4; Lipopolysaccharides; Lipoxygenase Inhibitors; Neutrophils; Passive Cutaneous Anaphylaxis; Platelet Activating Factor; Protein Synthesis Inhibitors; Pyrans; Quinolones; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Recombinant Fusion Proteins; Sialoglycoproteins; Skin; Triazoles; Zymosan

Experiments were designed to study the effect of systemically administered IL-5 on local eosinophil accumulation induced by the intradermal injection of the chemokine eotaxin in the guinea pig. Intravenous interleukin-5 (IL-5) stimulated a rapid and dramatic increase in the numbers of accumulating eosinophils induced by i.d.-injected eotaxin and, for comparison, leukotriene B4. The numbers of locally accumulating eosinophils correlated directly with a rapid increase in circulating eosinophils: circulating eosinophil numbers were 13-fold higher 1 h after intravenous IL-5 (18.3 pmol/kg). This increase in circulating cells corresponded with a reduction in the number of displaceable eosinophils recovered after flushing out the femur bone marrow cavity. Intradermal IL-5, at the doses tested, did not induce significant eosinophil accumulation. We propose that these experiments simulate important early features of the tissue response to local allergen exposure in a sensitized individual, with eosinophil chemoattractant chemokines having an important local role in eosinophil recruitment from blood microvessels, and IL-5 facilitating this process by acting remotely as a hormone to stimulate the release into the circulation of a rapidly mobilizable pool of bone marrow eosinophils. This action of IL-5 would be complementary to the other established activities of IL-5 that operate over a longer time course.

Topics: Animals; Bone Marrow; Bone Marrow Cells; Chemokine CCL11; Chemokines, CC; Chemotaxis, Leukocyte; Cytokines; Dose-Response Relationship, Drug; Drug Synergism; Eosinophil Peroxidase; Eosinophilia; Eosinophils; Guinea Pigs; Injections, Intradermal; Injections, Intravenous; Interleukin-5; Leukotriene B4; Male; Peroxidases; Skin

Human eosinophils produce upon treatment with 5-oxo-eicosatetraenoic acid or (5S,15S)-dihydroxyeicosatetraenoic acid a potent eosinophil-chemotactic eicosanoid, 5-oxo-15-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoi c acid (5-oxo-15-HETE). 5-Oxo-15-HETE induces human eosinophil (Eo) chemotaxis at nanomolar concentrations with an efficacy in vitro comparable to that seen for platelet activating factor. Comparison of Eo chemotactic activities of several structurally related eicosanoids with different substituents and/or double bound geometry led to the conclusion that maximal potency and efficacy of eosinophil-chemotactic and chemokinetic activity is present in 5-oxo-(6E,8Z,11Z,14Z)-eicosatetraenoic acid (5-oxo-ETE). The presence of a hydroxyl group at position C-15 is not necessary for potent chemotactic activity, whereas a geometric isomer having trans instead of cis double bond at C-atom 8, as well as esterified 5-oxo-ETE usually show a 5-10-fold lower potency. 5-Oxo-eicosanoids elicit a dose-dependent transient rise of intracellular Ca2+ levels in human Eos, however, in contrast to some other Eo chemotaxins do not induce degranulation. Cross-desensitization of Ca2+ mobilization and Eo chemotaxis revealed that the geometric isomers of 5-oxo-eicosanoids, 5(S)-HETE, and (5S,15S)-di-HETE cross-deactivate Eo responses to each other, whereas other, unrelated stimuli did not interfere with these lipids indicating that 5-oxo-eicosanoids activate Eos via a separate receptor.

Topics: Chemotactic Factors; Chemotaxis, Leukocyte; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Eicosanoic Acids; Eosinophilia; Eosinophils; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Indicators and Reagents; Kinetics; Leukotriene B4; N-Formylmethionine Leucyl-Phenylalanine; Platelet Activating Factor; Structure-Activity Relationship

The involvement of platelet activating factor (PAF) in antigen-induced bronchial hyperresponsiveness was investigated by the use of the PAF antagonists BN 52021 and BN 50730, in a guinea-pig model where sensitization and challenge were performed by aerosol. Male Hartley guinea-pigs were sensitized by two aerosol exposures at 48 hr intervals to a 0.9% NaCl solution (saline) containing 2 mg/ml ovalbumin for 30 min. Fifteen to 20 days later, guinea-pigs were challenged by exposure to five successive aerosols of increasing concentrations of ovalbumin (OA) or respectively, 10 microg/ml, 100 microg/ml, 1 mg/ml, 5 mg/ml and 10 mg/ml for 15 min each, or saline alone. Three to four hr and 18-24 hr after the aerosol challenge the guinea-pigs were prepared for recording of bronchopulmonary response and aerosol administrations were then generated with an ultrasonic nebulizer. The bronchopulmonary responses induced by successive 1-min aerosol bursts of acetylcholine (ACh) was assessed. As compared with saline-challenged guinea-pigs, an enhanced bronchopulmonary response to aerosol administration of cumulative doses of ACh was observed, 3-4 hr and 18-24 hr post-ovalbumin challenge. When the sensitized guinea-pigs were pretreated 1 hr before ovalbumin exposure with BN 52021 or BN 50730 (25 mg/kg, per os), a significant inhibition of the increase in the bronchopulmonary response to ACh was observed, both at 3-4 hr and 18-24 hr. Furthermore, when guinea-pigs were treated 3-4 hr after the ovalbumin exposure with BN 52021 or BN 50730, a significant inhibition of the hyperresponsiveness to ACh was recorded at 18-24 hr. A marked accumulation of eosinophils in the peribronchial regions was observed on histological preparations of lung specimens collected 4 hr or 24 hr after ovalbumin exposure. Pretreatment of the guinea-pigs by BN 50730 or BN 52021 did not modify the eosinophil accumulation in the peribronchial area. No significant difference in the number of eosinophils collected in the bronchoalveolar lavage fluid is observed, 24 hr post-ovalbumin challenge, under the pretreatment with BN 52021 or BN 50730. Pretreatment of guinea-pigs by BN 50730 or BN 52021 significantly reduced the PAF-induced (100 microg/ml) increase in eosinophil number in the peribronchial area. By contrast, they did not inhibit the eosinophilia induced by aerosol administration of LTB4 (5 microg/ml). These results suggest that the bronchial hyperresponsiveness observed in this study is associated with

Topics: Acetylcholine; Aerosols; Animals; Azepines; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Bronchoconstrictor Agents; Diterpenes; Eosinophilia; Ginkgo biloba; Ginkgolides; Guinea Pigs; Lactones; Leukotriene B4; Lung Diseases; Male; Molecular Structure; Ovalbumin; Plants, Medicinal; Platelet Activating Factor; Specific Pathogen-Free Organisms; Thienopyridines; Triazoles

We have attempted to determine whether interleukin-5 (IL-5), a cytokine that selectively affects eosinophil (as opposed to neutrophil) differentiation and activation, also modulates eosinophil migrational responses. Using a modified Boyden chemotaxis assay, IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) gave a weak locomotory response for eosinophils from normal nonatopic subjects (optimal at 10(-11), 10(-8), and 10(-9) mol/L, respectively), but not for eosinophils from subjects with an eosinophilia associated with asthma and/or allergic rhinitis. In contrast, IL-5 and IL-3 had no effect on neutrophils, while GM-CSF was chemotactic for neutrophils over a limited concentration range, optimal at 10(-8) mol/L. When eosinophils from normal subjects were incubated with IL-5 (10(-9) mol/L), the locomotory response to platelet-activating factor (PAF; 10(-8) mol/L, P less than .05), leukotriene B4 (LTB4; 10(-6) mol/L, P less than .01), and N-formyl-methionyl-leucyl-phenylalanine (FMLP; 10(-8) mol/L, P less than .01) was significantly enhanced. The percentage enhancement of eosinophil locomotion by IL-5 was greater for eosinophils from normal as compared with subjects with an eosinophilia associated with asthma (P less than .05 for PAF and LTB4; P less than .01 for FMLP). Preincubation of eosinophils from normal subjects with IL-5 (10(-9) mol/L) attenuated the subsequent locomotory response to IL-5 (10(-12) and 10(-11) mol/L, P less than .05). Therefore, the observed refractoriness of eosinophils from eosinophilic subjects to both directional migratory and priming effects of IL-5 in vitro, may reflect a deactivation process resulting from prior exposure in vivo. The selective priming of eosinophil but not neutrophil locomotion by IL-5 suggests that this cytokine may play a significant role in the preferential accumulation of eosinophils at sites of allergic inflammation.

Topics: Asthma; Chemotaxis, Leukocyte; Eosinophilia; Eosinophils; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-3; Interleukin-5; Leukotriene B4; N-Formylmethionine Leucyl-Phenylalanine; Platelet Activating Factor; Rhinitis

Topics: Allergens; Animals; Bronchi; Eosinophilia; Fatty Alcohols; Glycols; Leukotriene B4; Lung; Pulmonary Alveoli; Rats; Rats, Inbred BN; Tetrazoles

Peripheral-blood polymorphonuclear cells from 36 donors with or without eosinophilia were studied for their in vitro responsiveness towards a wide range of concentrations of leukotriene B4 (LTB4) and platelet-activating factor (PAF). The mean percentage of migrated eosinophils was 17.6 for PAF, 21.1 for LTB4, 20.1 for buffer controls with cells from eosinophil patients, and 1.1 for PAF, 8.9 for LTB4 and 3.2 for buffer control with noneosinophil donors. The quantitative response of eosinophils towards PAF was lower than that towards LTB4 on a molar basis. The data showed high interindividual variations for eosinophil responsiveness towards mediators and buffer and suggest disease-dependent alterations of receptor expression or of basic metabolic activity of eosinophils as possible reasons for this variability.

Topics: Cell Movement; Chemotaxis, Leukocyte; Eczema; Eosinophilia; Eosinophils; Humans; In Vitro Techniques; Leukotriene B4; Neutrophils; Platelet Activating Factor; Skin Diseases

Peripheral blood neutrophils and eosinophils from 70 patients and controls were studied for their in vitro chemotactic and chemokinetic responses towards synthetic leukotriene B4 (LTB4), 20-OH-LTB4 and 20-COOH-LTB4. All three factors induced chemotaxis and chemokinesis of cells. 20-OH-LTB4 was always less and 20-COOH-LTB4 even less active than the parent compound. Cells from patients with atopic eczema and T cell lymphoma moved less than cells from normal controls or from patients with psoriasis. In the presence of LTB4, 20-OH-LTB4 and buffer alone, more eosinophils than neutrophils moved to the lower side of the filter, while this did not occur with platelet activating factor as chemoattractant. Studies of neutrophil and eosinophil chemotaxis in the presence of LTB4 should therefore always take into account a high variability of the quantitative response which is donor and disease dependent.

Topics: Chemotaxis, Leukocyte; Dermatitis, Atopic; Eosinophilia; Eosinophils; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Leukotriene B4; Lymphoma; Neutrophils; Psoriasis

The arachidonic acid lipoxygenase metabolites of polymorphonuclear leukocyte (PMNL) preparations obtained from 31 subjects with eosinophilia (eosinophil content of PMNL preparations: 27.0%, 4-73, median with range) and 29 normal donors (4.5%, 0-15) were analyzed by reversed phase high performance liquid chromatography. More leukotriene (LT) C4 and 15-hydroxyeicosatetraenoic acid (HETE) (p less than 0.001) and less LTB4 (p less than 0.005) were found in eosinophil-rich preparations in comparison to controls on incubations with ionophore and arachidonic acid. In incubations with arachidonic acid alone, only small amounts of 5-lipoxygenase metabolites were produced by both groups, but the PMNL preparations from patients with eosinophilia showed higher capacity to release LTC4 and 15-HETE (p less than 0.005). In the eosinophil-rich preparations, the percentage of eosinophils correlated positively with the production of LTC4 and negatively with LTB4 (p less than 0.05, incubations with ionophore +/- arachidonic acid), and positively with 15-HETE (p less than 0.01, incubations with arachidonic acid +/- ionophore). Moreover the eosinophil-rich preparations produced more LTC4 per eosinophil in incubations with arachidonic acid alone (p less than 0.001) than normal PMNL preparations. The predominant release of LTC4 and 15-HETE by eosinophils was further confirmed by the analysis of bronchoalveolar lavage cells. Lavage cells containing eosinophils released LTC4 and 15-HETE while normal bronchoalveolar lavages, which were poor in eosinophils, did not produce detectable amount of LTC4 and 15-HETE. These results show that eosinophils release preferentially LTC4 and 15-HETE in contrast to LTB4 for the neutrophils.

Topics: Adolescent; Adult; Aged; Arachidonate 15-Lipoxygenase; Arachidonate 5-Lipoxygenase; Arachidonate Lipoxygenases; Arachidonic Acids; Child; Chromatography, High Pressure Liquid; Eosinophilia; Eosinophils; Female; Humans; Hydroxyeicosatetraenoic Acids; Leukocytes; Leukotriene B4; Macrophages; Male; Middle Aged; Neutrophils; Pulmonary Alveoli; Reference Values; SRS-A

Topics: Adolescent; Adult; Aged; Cellulitis; Eosinophilia; Female; Humans; Leukotriene B4; Male; Skin; Skin Diseases, Vesiculobullous; SRS-A

The formation of 5- and 15-lipoxygenase products of arachidonic acid metabolism was examined in human peripheral blood eosinophils obtained from five normal individuals and five patients with the hypereosinophilic syndrome (HES). Normal and HES eosinophils after stimulation with the calcium ionophore A23187 produced in comparable amounts leukotriene (LT)C4, LTD4, LTB4 and two of its isomers (5-(S),12-(R)-6-trans-LTB4 and 5-(S), 12-(S)-6-trans-LTB4), 15-hydroxy-eicosatetraenoic acid (HETE), 5,15-di-HETE and 8,15-di-HETE. No single lipoxygenase product predominated in the absence of added arachidonic acid whereas 15-HETE was the major product formed when either normal or HES eosinophils were stimulated with A23187 in the presence of added arachidonic acid (10(-4) M).

Topics: Arachidonate Lipoxygenases; Arachidonic Acids; Calcimycin; Chromatography, High Pressure Liquid; Eosinophilia; Eosinophils; Humans; Leukotriene B4; Lipoxygenase; SRS-A; Syndrome