| First Author | Zizza P | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 20 | Pages | 16849-59 |
| PubMed ID | 22393044 | Mgi Jnum | J:318076 |
| Mgi Id | MGI:6858179 | Doi | 10.1074/jbc.M111.309419 |
| Citation | Zizza P, et al. (2012) Phospholipase A2IValpha regulates phagocytosis independent of its enzymatic activity. J Biol Chem 287(20):16849-59 |
| abstractText | Group IValpha phospholipase A(2) (PLA(2)IValpha) is a lipolytic enzyme that catalyzes the hydrolysis of membrane phospholipids to generate precursors of potent inflammatory lipid mediators. Here, the role of PLA(2)IValpha in Fc receptor (FcR)-mediated phagocytosis was investigated, demonstrating that PLA(2)IValpha is selectively activated upon FcR-mediated phagocytosis in macrophages and that it rapidly translocates to the site of the nascent phagosome. Moreover, pharmacological inhibition of PLA(2)IValpha by pyrrophenone reduces particle internalization by up to 50%. In parallel, fibroblasts from PLA(2)IValpha knock-out mice overexpressing FcgammaRIIA and able to internalize IgG-opsonized beads show 50% lower phagocytosis, compared with wild-type cells, and transfection of PLA(2)IValpha fully recovers this impaired function. Interestingly, transfection of the catalytically inactive deleted PLA(2)IValpha mutant (PLA(2)IValpha(1-525)) and point mutant (PLA(2)IValpha-S228C) also promotes recovery of this impaired function. Finally, transfection of the PLA(2)IValpha C2 domain (which is directly involved in PLA(2)IValpha membrane binding), but not of PLA(2)IValpha-D43N (which cannot bind to membranes), rescues FcR-mediated phagocytosis. These data unveil a new mechanism of action for PLA(2)IValpha, which demonstrates that the membrane binding, and not the enzymatic activity, is required for PLA(2)IValpha modulation of FcR-mediated phagocytosis. |
