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/10⁷ cells of LTB₄ measured by radioimmunoassay. However, the maximum aggregation of PMNs achieved by exposure to LTB₄ (10⁻⁷M) was only 50% of that produced by maximally aggregating concentrations of PAF (10⁻⁷M). 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.