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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/FcεRI pathway, while only serosal mast cells are activated by basic secretagogues. We show that CD47 receptors are expressed on rat peritonea...

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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
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creator Sick, E
Niederhoffer, N
Takeda, K
Landry, Y
Gies, J.-P
description 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.
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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. 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Mol. Life Sci</addtitle><addtitle>Cell Mol Life Sci</addtitle><description>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. 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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
title Activation of CD47 receptors causes histamine secretion from mast cells
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