Analysis of Two Major Intracellular Phospholipases A(2) (PLA(2)) in Mast Cells Reveals Crucial Contribution of Cytosolic PLA(2)alpha, Not Ca2+-independent PLA(2)beta, to Lipid Mobilization in Proximal Mast Cells and Distal Fibroblasts

作者：Ueno Noriko; Taketomi Yoshitaka; Yamamoto Kei; Hirabayashi Tetsuya; Kamei Daisuke; Kita Yoshihiro; Shimizu Takao; Shinzawa Koei; Tsujimoto Yoshihide; Ikeda Kazutaka; Taguchi Ryo; Murakamia Makoto^*

来源：Journal of Biological Chemistry, 2011, 286(43): 37249-37263.

DOI：10.1074/jbc.M111.290312

Mast cells release a variety of mediators, including arachidonic acid (AA) metabolites, to regulate allergy, inflammation, and host defense, and their differentiation and maturation within extravascular microenvironments depend on the stromal cytokine stem cell factor. Mouse mast cells express two major intracellular phospholipases A(2) (PLA(2)s), namely group IVA cytosolic PLA(2) (cPLA(2)alpha) and group VIA Ca2+-independent PLA2 (iPLA(2)beta), and the role of cPLA(2)alpha in eicosanoid synthesis by mast cells has been well documented. Lipidomic analyses of mouse bone marrow-derived mast cells (BMMCs) lacking cPLA(2)alpha (Pla2g4a(-/-)) or iPLA(2)beta (Pla2g6(-/-)) revealed that phospholipids with AA were selectively hydrolyzed by cPLA(2)alpha, not by iPLA(2)beta, during Fc epsilon RI-mediated activation and even during fibroblast-dependent maturation. Neither Fc epsilon RI-dependent effector functions nor maturation-driven phospholipid remodeling was impaired in Pla2g6(-/-) BMMCs. Although BMMCs did not produce prostaglandin E-2 (PGE(2)), the AA released by cPLA(2)alpha from BMMCs during maturation was converted to PGE(2) by microsomal PGE synthase-1 (mPGES-1) in cocultured fibroblasts, and accordingly, Pla2g4a(-/-) BMMCs promoted microenvironmental PGE(2) synthesis less efficiently than wild-type BMMCs both in vitro and in vivo. Mice deficient in mPGES-1 (Ptges(-/-)) had an augmented local anaphylactic response. These results suggest that cPLA(2)alpha in mast cells is functionally coupled, through the AA transfer mechanism, with stromal mPGES-1 to provide anti-anaphylactic PGE(2). Although iPLA(2)beta is partially responsible for PGE(2) production by macrophages and dendritic cells, it is dispensable for mast cell maturation and function.

• 出版日期2011-10-28
• 单位河北医科大学