The involvement of adhesion molecules and lipid mediators in the adhesion of human platelets to eosinophils.
Platelet-leukocyte interactions represent an important determinant of the inflammatory response. Although mechanisms of platelet-neutrophil adhesion were studied extensively, little is known on the mechanisms of platelet-eosinophil interactions. The aim of the present study was to analyze the involvement of adhesion molecules and lipid mediators in platelet-eosinophil adhesion as compared to platelet-neutrophil adhesion. For that purpose human platelets, eosinophils and neutrophils were isolated and platelet-eosinophil and platelet-neutrophil adhesion induced by thrombin (30 mU/ml), LPS (0.01 microg/ml) and fMLP (1 microM) was quantified using the "rosettes" assay. The involvement of adhesion molecules such as selectin P, glycoprotein IIb/IIIa (GPIIb/IIIa) and lipid mediators such as of thromboxane A2 (TXA2), platelet activating factor (PAF) and cysteinyl leukotrienes (cysLTs) were studied using monoclonal antibodies and pharmacological inhibitors, respectively. Thrombin (30 mU/ml), LPS (0.01 microg/ml) and fMLP (1 microM) each of them induced platelet-eosinophil adhesion that was even more pronounced as compared with platelet-neutrophil adhesion induced by the same stimulus. Anti-CD62P antibody (1 microg/ml) and anti-GP IIb/IIIa antibody (abciximab-3 microg/ml) strongly inhibited platelet-eosinophil as well as platelet-neutrophil adhesion. Aspirin inhibited platelet-eosinophil adhesion, while MK 886-a FLAP inhibitor (10 microM), or WEB 2170-a PAF receptor antagonist (100 microM) were less active. On the other hand aspirin, MK 886 and WEB 2170 all three of them inhibited platelet-neutrophil adhesion. In summary, platelets adhered avidly to eosinophils both after activation of platelets by thrombin, eosinophils by fMLP or simultaneous activation of platelets and eosinophils by LPS. Similarly to platelet-neutrophil interaction adhesion of platelets to eosinophils involved not only adhesion molecules (selectin P, GPIIb/IIIa), but also lipid mediators such as TXA2. The involvement of PAF and cysteinyl leukotrienes in platelet-eosinophil adhesion was less pronounced as compared to platelet-neutrophil adhesion.
Jawień
J
J
Jagiellonian University Medical College, Kraków, Poland.
Lomnicka
M
M
Korbut
R
R
Chłopicki
S
S
D000077284:Abciximab; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology*; D019041:L-Selectin / Q000502:physiology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D019007:P-Selectin / Q000502:physiology; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011134:Polysaccharides / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology; D002722:Chlorobenzenes
D000077284:Abciximab; D000911:Antibodies, Monoclonal; D001241:Aspirin; D001381:Azepines; D015815:Cell Adhesion Molecules; D016861:Cyclooxygenase Inhibitors; D007140:Immunoglobulin Fab Fragments; D007211:Indoles; D018836:Inflammation Mediators; D019041:L-Selectin; D016859:Lipoxygenase Inhibitors; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D011134:Polysaccharides; D043562:Receptors, G-Protein-Coupled; D013928:Thromboxane A2; D014230:Triazoles; C039351:platelet activating factor receptor; C060893:MK-886; D002722:Chlorobenzenes; C007789:fucoidan; C063964:bepafant