Platelet-activating factor augments tumor necrosis factor and procoagulant activity.
Infusion of platelet activating factor (PAF) reproduces the host physiologic response to endotoxemia and sepsis. Tumor necrosis factor (TNF) and procoagulant activity (PCA) are two other potentially deleterious central inflammatory mediators produced in large quantities by tissue-fixed macrophages (M phi). The relationship, if any, between PAF and TNF or PCA production is unknown. Rabbit alveolar M phi were treated in vitro with PAF alone and prior to endotoxin (LPS). PAF alone had no effect on M phi PCA or TNF. PAF (10(-9)-10(-6) M) cotreatment enhanced M phi PCA and TNF levels in a dose response from two- to sixfold above that of LPS treatment alone. PAF (10(-6) M) pretreatment of M phi at T -4 to -6 hr produces an eight- to ninefold enhancement in both TNF and PCA levels. Thus, both coincubation and pretreatment or "priming" of the M phi with PAF prior to LPS stimulation greatly increase M phi production of PCA and TNF. The ability to augment the production of these two potent inflammatory mediators may explain in part the mechanism of action of PAF in vivo.
Maier
R V
RV
Department of Surgery, University of Washington, Seattle.
Hahnel
G B
GB
Fletcher
J R
JR
D000818:Animals; D001779:Blood Coagulation Factors / Q000096:biosynthesis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects*
D001779:Blood Coagulation Factors; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; C045072:macrophage procoagulant activity; D002118:Calcium