Activation of CD47 receptors causes histamine secretion from mast cells

• Published in: Cellular and molecular life sciences : CMLS 2009-04, Vol.66 (7), p.1271-1282
• Main Authors: Sick, E, Niederhoffer, N, Takeda, K, Landry, Y, Gies, J.-P
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Biochemistry; Biochemistry, Molecular Biology; Biomedical and Life Sciences; Biomedicine; CD47 Antigen - immunology; CD47 Antigen - physiology; Cell Biology; Cell Membrane - physiology; Cells; Cellular Biology; Cholesterol - physiology; Exocytosis; Glycosylphosphatidylinositols - metabolism; GTP-Binding Protein beta Subunits - immunology; GTP-Binding Protein beta Subunits - metabolism; GTP-Binding Protein gamma Subunits - immunology; GTP-Binding Protein gamma Subunits - metabolism; Histamine - biosynthesis; Histamine Release - physiology; In Vitro Techniques; Integrin beta Chains - immunology; Intercellular Signaling Peptides and Proteins; Life Sciences; Male; Mast Cells - drug effects; Mast Cells - metabolism; Membrane Microdomains - physiology; Oligopeptides - pharmacology; Peptides; Peptides - pharmacology; Pertussis Toxin - pharmacology; Protein Multimerization; Proteins; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Research Article; Rodents; Spermine - pharmacology; Studies; Toxins; Type C Phospholipases - metabolism; Wasp Venoms - pharmacology
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-009-8778-2

Mast cells play pivotal roles in allergic and inflammatory processes via distinct activation pathways. Mucosal and serosal mast cells are activated by the IgE/FcεRI 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 βγ dimer of a Gi 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/Gi 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/Gi protein complex.