Leukotriene B-4 augments neutrophil phagocytosis of Klebsiella pneumoniae

Neutrophils play a critical role in the clearance of bacteria from the lung and other organs by their capacity for phagocytosis and killing. Previousl y, we identified an important role for the leukotrienes in rat alveolar mac rophage phagocytosis of Klebsiella pneumoniae. In this report, we explored the possibility that the leukotrienes play an important role in phagocytosi s by neutrophils as well. Inhibition of endogenous leukotriene synthesis by 5-lipoxygenase knockout in mice or by pharmacologic means in human periphe ral blood neutrophils attenuated phagocytosis of opsonized K. pneumoniae. R educed phagocytosis was also observed in human neutrophils pretreated,vith a leukotriene B-4 receptor but not a cysteinyl-leukotriene receptor antagon ist. While leukotriene B-4 reconstituted defective phagocytosis in leukotri ene-deficient neutrophils and enhanced phagocytosis in neutrophils capable of leukotriene synthesis, leukotriene C-4, leukotriene D-4, 5-hydroperoxyei cosatetraenoic acid, and 5-oxo-eicosatetraenoic acid were ineffective. To d etermine the opsonin dependence of the leukotriene B-4 augmentation of phag ocytosis, we assessed the ability of leukotriene B-4 to modulate neutrophil phagocytosis and the adherence of sheep erythrocytes opsonized with immuno globulin G or the complement fragment C3bi. While leukotriene B-4 augmented both Fc receptor- and complement receptor-mediated phagocytosis, increased adherence to leukotriene B-4-treated neutrophils was limited to complement opsonized targets. In conclusion, we have identified a novel role for leuk otriene B-4 in the augmentation of neutrophil phagocytosis mediated by eith er the Fc or complement receptor.