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Cell Mol Life Sci. 2009 Apr;66(7):1271-82. doi: 10.1007/s00018-009-8778-2.

Activation of CD47 receptors causes histamine secretion from mast cells.

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  • 1CNRS UMR 7213, Laboratoire de Biophotonique et Pharmacologie, Facult√© de Pharmacie, Universit√© de Strasbourg, 74 Route du Rhin, BP 60024, 67401 Illkirch, France. esick@pharma.u-strasbg.fr

Abstract

Mast cells play pivotal roles in allergic and inflammatory processes via distinct activation pathways. Mucosal and serosal mast cells are activated by the IgE/FcepsilonRI pathway, while only serosal mast cells are activated by basic secretagogues. We show that CD47 receptors are expressed on rat peritoneal mast cells. 4N1K, a peptide agonist of CD47, rapidly caused exocytosis. Such exocytosis required increased intracellular calcium and was inhibited by pertussis toxin and an antibody against the betagamma dimer of a G(i) protein. Cooperation with integrins and glycosylphosphatidylinositol-anchored proteins was necessary, since anti-integrin antibodies and pretreatment with phosphatidylinositol-phospholipase C reduced exocytosis. Depletion of membrane cholesterol inhibited exocytosis and decreased CD47 in lipid rafts, consistent with a CD47/integrin/G(i) protein complex being located in rafts. An anti-CD47 antibody inhibited exocytosis induced by 4N1K and by mastoparan and spermine, suggesting that basic secretagogues might target CD47. We propose that 4N1K-stimulated mast cell exocytosis involves a CD47/integrin/G(i) protein complex.

PMID:
19205621
[PubMed - indexed for MEDLINE]
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