Cytosolic Phospholipase A2 Translocates to Forming Phagosomes during Phagocytosis of Zymosan in Macrophages

Milena Girotti, John H. Evans, Danielle Burke, Christina C. Leslie

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Resident tissue macrophages mediate early innate immune responses to microbial infection. Cytosolic phospholipase A2α (cPLA 2α) is activated in macrophages during phagocytosis of non-opsonized yeast (zymosan) triggering arachidonic acid release and eicosanoid production. cPLA2α translocates from cytosol to membrane in response to intracellular calcium concentration ([Ca 2+]i) increases. Enhanced green fluorescent protein (EGFP)-cPLA2α translocated to forming phagosomes, surrounding the zymosan particle by 5 min and completely overlapping with early endosome (Rab5) and plasma membrane (F4/80) markers but only partially overlapping with resident endoplasmic reticulum proteins (GRP78 and cyclooxygenase 2). EGFP-cPLA2α also localized to membrane ruffles during phagocytosis. Zymosan induced an initial high amplitude calcium transient that preceded particle uptake followed by a low amplitude sustained calcium increase. Both phases were required for optimal phagocytosis. Extracellular calcium chelation prevented only the sustained phase but allowed a limited number of phagocytic events, which were accompanied by translocation of cPLA 2α to the phagosome although [Ca2+]i, remained at resting levels. The results demonstrate that cPLA 2α targets the phagosome membrane, which may serve as a source of arachidonic acid for eicosanoid production.

Original languageEnglish (US)
Pages (from-to)19113-19121
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number18
DOIs
StatePublished - Apr 30 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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