Polymorphonuclear leukocyte-derived O2-reactive species activate primed platelets in human whole blood.
The activation of human platelets by polymorphonuclear leukocytes (PMN) was investigated in human whole blood challenged with "priming" concentrations of arachidonic acid or collagen in the presence or absence of N-formyl-Met-Leu-Phe (FMLP), a selective activator of PMN. With the use of arachidonic acid or collagen alone at priming concentrations or FMLP alone, no platelet response was observed. In contrast, FMLP in combination with arachidonic acid or collagen caused irreversible platelet aggregation with thromboxane A2 production. Platelet response to FMLP-activated PMN was enhanced by superoxide dismutase and blocked by catalase or the NADPH oxidase inhibitor diphenyliodonium, suggesting a role for the O2-.-H2O2 system in this cellular interaction. This was corroborated by experiments with exogenously added H2O2, which mimicked FMLP effects in the activation of primed platelets in whole blood. The present investigation indicates that platelets primed with minute amounts of arachidonic acid or collagen can be activated, in human whole blood, by oxygen-reactive species released by PMN.
Praticò
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D
University of Rome La Sapienza, Institute of 1st Clinical Medicine, Italy.
Iuliano
L
L
Alessandri
C
C
Camastra
C
C
Violi
F
F
D016718:Arachidonic Acid / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D013928:Thromboxane A2 / Q000096:biosynthesis
D001713:Biphenyl Compounds; D009861:Onium Compounds; C031291:diphenyliodonium; D016718:Arachidonic Acid; D013928:Thromboxane A2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003094:Collagen; D006861:Hydrogen Peroxide