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A novel calcium‐dependent proapoptotic effect of annexin 1 on human neutrophils
Author(s) -
Solito Egle,
Kamal Ahmad,
Russo-Marie Francoise,
Buckingham Julia C.,
Marullo Stefano,
Perretti Mauro
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0941fje
Subject(s) - annexin a1 , annexin , apoptosis , microbiology and biotechnology , intracellular , chemotaxis , inflammation , chemistry , dephosphorylation , calcium in biology , phosphorylation , biology , immunology , biochemistry , receptor , phosphatase
The glucocorticoid‐inducible protein annexin (ANXA) 1 is an anti‐inflammatory mediator that down‐regulates the host response. Endogenously, ANXA1 is released in large amounts from adherent polymorphonuclear neutrophils (PMN) and binds to their cell surface to inhibit their extravasation into inflamed tissues. The present study determined the effects of exogenous ANXA1 on several functions of human PMN in vitro. Addition of 0.1–1 µM human recombinant ANXA1 to the PMN provoked rapid and transient changes in intracellular Ca 2+ concentrations that were blocked by the Ca 2+ channel inhibitor SKF‐96365. Although ANXA1 did not affect oxidant production and only minimally affected PMN chemotactic properties, the ANXA1‐promoted Ca 2+ influx was associated with two important functional effects: shedding of L‐selectin and acceleration of PMN apoptosis. The latter effect was confirmed using three distinct technical procedures, namely, cell cycle, Hoechst staining, and ANXA5 binding assay. ANXA1‐induced PMN apoptosis was insensitive to inhibitors of L‐selectin shedding, whereas it appeared to be associated with dephosphorylation of the proapoptotic intracellular mediator BAD. In conclusion, exogenous ANXA1 displayed selective actions on human PMN. We propose that the new proapoptotic effect reported here may be part of the spectrum of ANXA1‐mediated events involved in the resolution of acute inflammation.