Activation of CD47 receptors causes histamine secretion from mast cells.
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.
Sick
E
E
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
Niederhoffer
N
N
Takeda
K
K
Landry
Y
Y
Gies
J-P
JP
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
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