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.
Lee
Ha Young
HY
Medical Research Center for Cancer Molecular Therapy, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
Kim
Mi-Kyoung
MK
Park
Kyoung Sun
KS
Shin
Eun Ha
EH
Bae
Yoe-Sik
YS
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*
D007975:Leukotriene B4; D010741:Phospholipases A; D054500:Group IB Phospholipases A2; C516202:PLA2G1B protein, human; D054467:Phospholipases A2