Platelet-activating factor-induced enhancement of superoxide anion generation in guinea-pigs.
We studied whether platelet-activating factor (PAF) enhances superoxide anion (O2-) generation in guinea-pigs. The production of O2- was assayed by chemiluminescence, using a Cypridina luciferin analog as a highly sensitive and specific probe for O2-. I.v. administered PAF significantly enhanced phorbol myristate acetate- or N-formyl-methionyl-leucyl-phenylalanine-induced O2- generation by guinea-pig alveolar macrophages or by polymorphonuclear leukocytes in a dose-dependent manner. The priming effect of PAF on O2- generation was maximal in cells harvested 5 min after administration of PAF. These responses were completely inhibited by administration of WEB 2086, a specific PAF receptor antagonist, or ONO-3708, a specific thromboxane A2 receptor antagonist, suggesting that the effects were mediated through the PAF receptor and thromboxane A2 generation. PAF might contribute to airway inflammation by enhancing O2- formation in addition to exerting other effects such as smooth muscle contraction or microvascular leakage.
Kato
M
M
Department of Pediatrics, Gunma University School of Medicine, Japan.
Tokuyama
K
K
Morikawa
A
A
Kuroume
T
T
Barnes
P J
PJ
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008163:Luminescent Measurements; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled; D017482:Receptors, Thromboxane / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017482:Receptors, Thromboxane; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; D013481:Superoxides; D013928:Thromboxane A2; C049855:ONO 3708