Leukotriene B4-Mediated Release of Antimicrobial Peptides against Cytomegalovirus Is BLT1 Dependent

Leukotriene B4 (LTB4) is a potent lipid mediator of inflammation that possesses antiviral activities. Here we provide evidence that LTB4-mediated defense against in vitro cytomegalovirus (CMV) infection of human leukocytes involves activation of the high-affinity LTB4 receptor (BLT1) and neutrophil degranulation. Treatment of CMV-infected peripheral blood leukocytes with LTB4 (10 nM) leads to a significant reduction in viral titers. This activity involves neutrophil activation through the BLT1 receptor, because no reduction in viral titers was observed after neutrophil depletion from cellular preparation or when leukocytes were pretreated with the BLT1 antagonist U75302. Direct stimulation of neutrophils with LTB4 (in the presence or absence of CMV) leads to the release of myeloperoxidase, α-defensins, eosinophil-derived neurotoxin, and the human cathelicidin LL-37 in a BLT1-dependent manner. LTB4 does not act exclusively on the secretion of preformed antimicrobial peptides, but also acts on the synthesis...