Regulation of cytosolic phospholipase A 2 phosphorylation by proteolytic cleavage of annexin A1 in activated mast cells

Joon Hyun Kwon, Jea Hwang Lee, Ki Soon Kim, Youn Wook Chung, Ick Young Kim

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Annexin A1 (ANXA1) is cleaved at the N terminal in some activated cells, such as macrophages, neutrophils, and epithelial cells. We previously observed that ANXA1 was proteolytically cleaved in lung extracts prepared from a murine OVA-induced asthma model. However, the cleavage and regulatory mechanisms of ANXA1 in the allergic response remain unclear. In this study, we found that ANXA1 was cleaved in both Ag-induced activated rat basophilic leukemia 2H3 (RBL-2H3) cells and bone marrow-derived mast cells. This cleavage event was inhibited when intracellular Ca 2+ signaling was blocked. ANXA1-knockdown RBL-2H3 cells produced a greater amount of eicosanoids with simultaneous upregulation of cytosolic phospholipase A 2 (cPLA 2) activity. However, there were no changes in degranulation activity or cytokine production in the knockdown cells. We also found that cPLA 2 interacted with either full-length or cleaved ANXA1 in activated mast cells. cPLA 2 mainly interacted with full-length ANXA1 in the cytosol and cleaved ANXA1 in the membrane fraction. In addition, introduction of a cleavage-resistant ANXA1 mutant had inhibitory effects on both the phosphorylation of cPLA 2 and release of eicosanoids during the activation of RBL-2H3 cells and bone marrow-derived mast cells. These data suggest that cleavage of ANXA1 causes proinflammatory reactions by increasing the phosphorylation of cPLA 2 and production of eicosanoids during mast-cell activation.

Original languageEnglish
Pages (from-to)5665-5673
Number of pages9
JournalJournal of Immunology
Volume188
Issue number11
DOIs
Publication statusPublished - 2012 Jun 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Regulation of cytosolic phospholipase A <sub>2</sub> phosphorylation by proteolytic cleavage of annexin A1 in activated mast cells'. Together they form a unique fingerprint.

  • Cite this