Clearance of group X secretory phospholipase A2 via mouse phospholipase A2 receptor

摘要

>Given the potent hydrolyzing activity toward phosphatidylcholine, group X secretory phospholipase A₂ (sPLA₂-X) elicits a marked release of arachidonic acid linked to the potent production of lipid mediators in various cell types. We have recently shown that sPLA₂-X can also act as a ligand for mouse phospholipase A₂ receptor (PLA₂R). Here, we found that sPLA₂-X was internalized and degraded via binding to PLA₂R associated with the diminished prostaglandin E₂ (PGE₂) formation in PLA₂R-expressing Chinese hamster ovary (CHO) cells compared to CHO cells. Indirect immunocytochemical analysis revealed that internalized sPLA₂-X was co-localized with PLA₂R in the punctate structures in PLA₂R-expressing CHO cells. Moreover, in mouse osteoblastic MC3T3-E₁ cells that endogenously express the PLA₂R, the internalized sPLA₂-X was localized in lysosomes. These findings demonstrate that PLA₂R acts as a clearance receptor for sPLA₂-X to suppress its strong enzymatic activity.