Phospholipase A2IVα regulates phagocytosis independent of its enzymatic activity

Pasquale Zizza, Cristiano Iurisci, Matteo Bonazzi, Pascale Cossart, Christina C. Leslie, Daniela Corda, Stefania Mariggio

Research output: Contribution to journalArticlepeer-review


Group IVα phospholipase A2 (PLA2IVα) is a lipolytic enzyme that catalyzes the hydrolysis of membrane phospholipids to generate precursors of potent inflammatory lipid mediators. Here, the role of PLA2IVα in Fc receptor (FcR)-mediated phagocytosis was investigated, demonstrating that PLA2IVα 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 PLA2IVα by pyrrophenone reduces particle internalization by up to 50%. In parallel, fibroblasts from PLA 2IVα knock-out mice overexpressing FcγRIIA and able to internalize IgG-opsonized beads show 50% lower phagocytosis, compared with wild-type cells, and transfection of PLA2IVα fully recovers this impaired function. Interestingly, transfection of the catalytically inactive deleted PLA2IVαmutant (PLA2IVα(1-525) ) and point mutant (PLA2IVα- S228C) also promotes recovery of this impaired function. Finally, transfection of the PLA2IVα C2 domain (which is directly involved in PLA2IVα membrane binding), but not of PLA2IVα-D43N (which cannot bind to membranes), rescues FcR-mediated phagocytosis. These data unveil a new mechanism of action for PLA2IVα, which demonstrates that the membrane binding, and not the enzymatic activity, is required for PLA 2IVα modulation of FcR-mediated phagocytosis.

Original languageEnglish
Pages (from-to)16849-16859
Number of pages11
JournalJournal of Biological Chemistry
Issue number20
Publication statusPublished - May 11 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)


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