Obligatory role of lipid mediators in platelet-neutrophil adhesion.
Platelet-neutrophil interactions play an important role in thrombotic and inflammatory responses. Although it is well known that adhesion of platelets to neutrophils requires interactions of adhesion molecules on platelets such as P-selectin, or GPIIb/IIIa with their counterparts on neutrophils, little is known on the role of lipid mediators in this response. Here we studied involvement of thromboxane (TX) A2, platelet activating factor (PAF) and cysteinyl leukotrienes (cysLTs) in the mechanisms of platelet-neutrophil adhesion that was induced by thrombin (10-100 mU/ml), fMLP (0.01-1 microM) or LPS (0.001-100 microg/ml). All three stimulators in a concentration- and time-dependent manner induced platelet-neutrophil adhesion as quantified by the method of Jungi et al. [Blood 67(3) (1986) 629]. Platelet-neutrophil adhesion induced by each of the three activators was inhibited by blocking antibodies towards P-selectin, GPIIb/IIIa or CD18, but it was not affected by anti-E selectin antibody. Moreover, platelet-neutrophil adhesion induced by thrombin, fMPL or LPS was inhibited by the inhibitor of cyclooxygenase (aspirin), by TXA2 synthase inhibitor (camonagrel), by PAF receptor antagonist (WEB 2170), by the inhibitor of FLAP (MK 886) and by cysLTs receptors antagonist (MK 571). On the other hand, the selective inhibitor of COX-2 (rofecoxib) as well as the inhibitor of cytochrome P450-dependent monoxygenase (17-ODYA) were ineffective. In summary, adhesion of platelets to neutrophils is regulated not only by specific interaction between adhesion molecules on platelets and neutrophils, but also by lipid mediators such as TXA2, PAF and cysLTs released upon activation of platelets or/and neutrophils.
Department of Pharmacology, Jagiellonian University, 31-531 Cracow, 16 Grzegorzecka, Poland. mfschlop@cyf-kr.edu.pl
Stefan
S
Chlopicki
Magdalena
M
Lomnicka
Richard J
RJ
Gryglewski
D001792:Blood Platelets; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006487:Hemostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism*; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000378:metabolism*; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism*
D018836:Inflammation Mediators; D015289:Leukotrienes; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D013928:Thromboxane A2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013917:Thrombin