title: Activation of CD47 receptors causes histamine secretion from mast cells.
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.
authors.affiliation: CNRS UMR 7213, Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg, 74 Route du Rhin, BP 60024, 67401 Illkirch, France. esick@pharma.u-strasbg.fr
authors.forename: E
authors.initials: E
authors.lastname: Sick
authors.forename: N
authors.initials: N
authors.lastname: Niederhoffer
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: Y
authors.initials: Y
authors.lastname: Landry
authors.forename: J-P
authors.initials: JP
authors.lastname: Gies
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D051928:CD47 Antigen / Q000276:immunology / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D002784:Cholesterol / Q000502:physiology; D005089:Exocytosis; D044387:GTP-Binding Protein beta Subunits / Q000276:immunology / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000276:immunology / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006632:Histamine / Q000096:biosynthesis*; D006636:Histamine Release / Q000502:physiology*; D066298:In Vitro Techniques; D039641:Integrin beta Chains / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D021962:Membrane Microdomains / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D055503:Protein Multimerization; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism; D014862:Wasp Venoms / Q000494:pharmacology
chemical_list: C120273:4N1K peptide; D000911:Antibodies, Monoclonal; D051928:CD47 Antigen; C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D017261:Glycosylphosphatidylinositols; D039641:Integrin beta Chains; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; D017382:Reactive Oxygen Species; D014862:Wasp Venoms; D013096:Spermine; C037500:mastoparan; D006632:Histamine; D002784:Cholesterol; D037342:Pertussis Toxin; D010738:Type C Phospholipases