Group IB secretory phospholipase A2 stimulates leukotriene B4 production by a unique mechanism in human neutrophils.

We found that group IB secretory phospholipase A(2) (sPLA(2)-IB) stimulates leukotriene B4 (LTB4) production in the absence of cytochalasin B in human neutrophils. Although LTB4 production has been reported to be associated with arachidonic acid release, the exogenous addition of sPLA(2)-IB did not induce this release from human neutrophils, suggesting that sPLA(2)-IB stimulates LTB4 production without affecting arachidonic acid. Moreover, the intracellular signaling events induced by sPLA(2)-IB included an increase in intracellular Ca(2+), which is required for LTB4 production. sPLA(2)-IB also stimulated mitogen-activated protein kinase ERK, but its activity was not required for LTB4 production. In terms of functional aspects, the supernatant of sPLA(2)-IB-stimulated human neutrophils caused chemotactic migration, which was almost completely inhibited by preincubating these cells with three different 5-lipoxygenase inhibitors (MK-886, AA-861, or NDGA). Taken together, we suggest that sPLA(2)-IB plays a role in the modulation of inflammatory and immune responses by inducing LTB4 production in human neutrophils.