Evidence for a dual pathway in platelet activating factor-induced aggregation of rat polymorphonuclear leucocytes.
The purpose of this study was to determine the role, if any, of Leukotriene B4 (LTB4) in Platelet Activating Factor (PAF)-induced aggregation of rat polymorphonuclear leucocytes (PMNs). Exposure of rat PMNs to 10(-7) M PAF resulted in the release of 4.5 +/- 0.7 ng/10(7) cells of LTB4 measured by radioimmunoassay. However, the maximum aggregation of PMNs achieved by exposure to LTB4 (10(-7)M) was only 50% of that produced by maximally aggregating concentrations of PAF (10(-7)M). 5-Lipoxygenase inhibitors, BW755c and Nafazatrom at concentrations that completely abolished LTB4 synthesis inhibited the aggregation induced by PAF only by 40% and 50% respectively. Furthermore, desensitisation experiments revealed that the aggregatory response of PMNs to PAF was only partially refractory to prior treatment with LTB4 whereas the aggregatory response to LTB4 was completely refractory to prior treatment with PAF. These results suggest that PAF-induced aggregation of rat PMNs is in part mediated by LTB4 and in part directly by an as yet unidentified mechanism.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000494:pharmacology / Q000502:physiology*; D016859:Lipoxygenase Inhibitors; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D047069:Pyrazolones; D051381:Rats; D011919:Rats, Inbred Strains
D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D011720:Pyrazoles; D047069:Pyrazolones; D007975:Leukotriene B4; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; C018845:nafazatrom