Leukotriene B4 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. Previously, we identified an important role for the leukotrienes in rat alveolar macrophage phagocytosis of Klebsiella pneumoniae. In this report, we explored the possibility that the leukotrienes play an important role in phagocytosis by neutrophils as well. Inhibition of endogenous leukotriene synthesis by 5-lipoxygenase knockout in mice or by pharmacologic means in human peripheral blood neutrophils attenuated phagocytosis of opsonized K. pneumoniae. Reduced phagocytosis was also observed in human neutrophils pretreated with a leukotriene B4 receptor but not a cysteinyl-leukotriene receptor antagonist. While leukotriene B4 reconstituted defective phagocytosis in leukotriene-deficient neutrophils and enhanced phagocytosis in neutrophils capable of leukotriene synthesis, leukotriene C4, leukotriene D4, 5-hydroperoxyeicosatetraenoic acid, and 5-oxo-eicosatetraenoic acid were ineffective. To determine the opsonin dependence of the leukotriene B4 augmentation of phagocytosis, we assessed the ability of leukotriene B4 to modulate neutrophil phagocytosis and the adherence of sheep erythrocytes opsonized with immunoglobulin G or the complement fragment C3bi. While leukotriene B4 augmented both Fc receptor- and complement receptor-mediated phagocytosis, increased adherence to leukotriene B4-treated neutrophils was limited to complement opsonized targets. In conclusion, we have identified a novel role for leukotriene B4 in the augmentation of neutrophil phagocytosis mediated by either the Fc or complement receptor.
Mancuso
P
P
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0642, USA.
Nana-Sinkam
P
P
Peters-Golden
M
M
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D006801:Humans; D007711:Klebsiella pneumoniae / Q000276:immunology*; D007975:Leukotriene B4 / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects*; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors
D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase