Abstract
Mammals possess various types of secretory phospholipase A2, which differ in the primary structure and tissue distribution. The phosholipase A2 receptor (PLA2R) recognizes group IB phospholipase A2 (PLA2-IB) and mediates the PLA2-IB-induced biological responses in non-digestive organs, including eicosanoid production and contraction of airway smooth muscles. In this study, we generated PLA2R-deficient mice to define its biological roles further. These mice are viable, fertile, and without evident histopathological abnormalities. There was no difference in the clearance of circulating PLA2-IB between wild-type and mutant mice. After challenge with bacterial lipopolysaccharide (LPS), PLA2R-deficient mice exhibited longer survival than wild-type mice. The mutant mice were also resistant to lethal effects of exogenous PLA2-IB after sensitization with sublethal dose of LPS. The plasma levels of tumor necrosis factor-alpha and interleukin-1beta elevated after LPS treatment were significantly reduced in mutant mice compared with wild-type mice. These findings suggest a potential role of PLA2R in the progression of endotoxic shock.
Highlights
Phospholipase A2 (PLA2)1 comprises a diverse family of enzymes that cleave the sn-2 fatty acyl ester bond of glycerophospholipids to yield a free fatty acid and a lysophospholipid [1, 2]
Recent studies have demonstrated a variety of biological responses to PLA2-IB mediated via PLA2R in nondigestive organs, including cell proliferation [18], cell invasion [19], chemokinesis [20], eicosanoid production [21, 22], airway and vascular smooth muscle contraction [23, 24], and fertilization [25]
For the past three decades, PLA2-IB has been thought to act as a digestive enzyme, given its abundance in digestive organs including the pancreas [7]
Summary
Phospholipase A2 (PLA2)1 comprises a diverse family of enzymes that cleave the sn-2 fatty acyl ester bond of glycerophospholipids to yield a free fatty acid and a lysophospholipid [1, 2]. Mice deficient for PLA2R exhibited resistance to lethal effects of lipopolysaccharide (LPS), suggesting that PLA2R plays a role in promoting endotoxic shock.
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