title: Group IB secretory phospholipase A2 stimulates leukotriene B4 production by a unique mechanism in human neutrophils.
abstract: 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.
authors: Medical Research Center for Cancer Molecular Therapy, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
authors: Ha Young
authors: HY
authors: Lee
authors: Mi-Kyoung
authors: MK
authors: Kim
authors: Kyoung Sun
authors: KS
authors: Park
authors: Eun Ha
authors: EH
authors: Shin
authors: Yoe-Sik
authors: YS
authors: Bae
mesh_terms: D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D054500:Group IB Phospholipases A2; D006801:Humans; D007975:Leukotriene B4 / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D007975:Leukotriene B4; D010741:Phospholipases A; D054500:Group IB Phospholipases A2; C516202:PLA2G1B protein, human; D054467:Phospholipases A2