Platelet activating factor is a potent stimulant of the production of active oxygen species by human monocyte-derived macrophages.
Platelet activating factor (PAF; C16), 1-O-Hexadecyl-2-acetyl-sn-glycero-3-phosphorylcholine) stimulated the production of active oxygen species by human monocyte-derived macrophages in culture. An optimal response was observed at a concentration of 13 microM PAF with half-maximal stimulation at 5 microM. The generation of superoxide ion (O2-) and hydrogen peroxide (H2O2) in response to PAF was inhibited specifically by a PAF-antagonist (1-O-Hexadecyl-2-acetyl-sn-glycero-3-phospho (N,N,N,-trimethyl) hexanolamine; such generation varied with the degree of maturation of cultured monocytes into macrophages. Production of active oxygen species increased progressively to reach a maximal level between days 4 to 6 of culture and remained maximal to day 12, after which it decreased progressively. Phorbol 12-myristate-13-acetate (PMA) and opsonized zymosan also stimulated generation of O2- and H2O2. PAF was however distinguished by its potent capacity to stimulate O2- and H2O2 production even at late stages of macrophage maturation (18 days), at which time both PMA and zymosan lacked significant effect. These findings suggest that PAF is a factor of potential relevance to the inflammatory role of the macrophage in atherogenesis.
Rouis
M
M
Groupe de Recherches INSERM sur les Lipoprotéines, Hôpital de la Pitié, Paris, France.
Nigon
F
F
Chapman
M J
MJ
D002454:Cell Differentiation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*
D010972:Platelet Activating Factor; D013481:Superoxides; C037145:1-hexadecyl-2-acetyl-glycero-3-phosphocholine; D006861:Hydrogen Peroxide