Elsevier

Immunopharmacology

Volume 27, Issue 1, January–February 1994, Pages 1-11

Review article
Peptidergic pathway in human skin and rat peritoneal mast cell activation

https://doi.org/10.1016/0162-3109(94)90002-7Get rights and content

Abstract

The common pathway of heterogenous mast cell activation as mediated by antigens is through the cross-linking of IgE bound to FcϵRI receptors. The peptidergic pathway of mast cell activation, achieved by cationic secretagogues, is restricted to “serosal” mast cells, the experimental models being rat peritoneal and human skin mast cells. Cationic secretagogues include positively charged peptides but also various amines such as compound 48/80 and natural polyamines. An early intracellular event of this pathway is the activation of pertussis toxin-sensitive G proteins. The correlation observed between the ability of basic compounds to trigger mast cell exocytosis and their potency to activate purified G proteins strongly suggests that cationic compounds activate mast cell G proteins via a receptor-independent but membrane-assisted process. In this paper, alternative mechanisms are discussed. The consequence of G protein stimulation is the activation of phospholipase C with an increase in inositol triphosphates. Natural polyamines are relatively poor triggers of mast cells (10−4 to 10−2 M). Neuropeptides such as substance P, neuropeptide Y or vasoactive intestinal peptide, peptidic hormones such as kinins, and venoms such as mastoparan and mast cell degranulating peptide, are all active in a concentration range from 10−7 to 10−4 M. The cationic anaphylatoxin C3a also stimulates mast cells at concentrations below precursor complement C3 blood levels. The component C3 of the complement system is one of only a few plasma proteins having activation fragments (i.e. C3a) that can be generated at micromolar levels. The effects of basic secretagogues defines a peptidergic pathway of mast cell activation, which represents a potentially toxic process considering the tissue effects caused by exogenous basic compounds such as venom peptides and certain amine containing drugs. Peptidergic activation of mast cells may also be a pathophysiological process having an important role in neurogenic inflammation and in diseases involving extensive activation of the blood complement cascade.

References (69)

  • T. Higashijima et al.

    Mastoparan, a peptide toxin from wasp venom, mimics receptors by activating GTP-binding regulatory proteins (G proteins)

    J Biol Chem

    (1988)
  • T. Higashijima et al.

    Regulation of Gi and Go by mastoparan, related amphiphilic peptides, and hydrophobic amines

    J Biol Chem

    (1990)
  • T. Higashijima et al.

    Mapping of the mastoparan-binding site on G proteins

    J Biol Chem

    (1991)
  • M. Mousli et al.

    G Protein activation: a receptor-independent mode of action for amphiphilic neuropeptides and venom peptides

    Trends Pharmacol Sci

    (1990)
  • M. Mousli et al.

    Direct activation of GTP-binding regulatory proteins (G proteins) by substance P and compound 48/80

    FEBS Lett

    (1990)
  • M. Mousli et al.

    Evidence for the interaction of mast-cell degranulating peptide (MCD) with pertussis toxin-sensitive G proteins in mast cells

    Eur J Pharmacol (Molec Pharmacol Sec)

    (1991)
  • H. Mukai et al.

    G protein antagonists, a novel hydrophobic peptide compete with receptor for G protein binding

    J Biol Chem

    (1992)
  • T. Nakamura et al.

    Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin

    J Biol Chem

    (1985)
  • M. Nesmeyanova et al.

    Participation of acid phospholipids in protein translocation across the bacterial cytoplasmic membrane

    FEBS Lett

    (1989)
  • F.L. Pearce

    Mast cell heterogeneity

    Trends Pharmacol Sci

    (1983)
  • J.W. Putney

    A model for receptor-regulated calcium entry

    Cell Calcium

    (1986)
  • H. Takemura et al.

    Activation of calcium entry by the tumor promoter, thapsigargin, in rat parotid acinar cells. Evidence that an intracellular calcium pool, and not an inositol phosphate regulates calcium fluxes at the plasma membrane

    J Biol Chem

    (1989)
  • H. Takemura et al.

    The thapsigargin-sensitive intracellular Ca2+ pool is more important in plasma membrane Ca2+ entry than the IP3 sensitive intracellular Ca2+ pool in neuronal cells

    Biochem Biophys Res Commun

    (1991)
  • U. Tomita et al.

    Direct activation of GTP-binding proteins by venom peptides that contain cationic cluster within their alpha-helical structures

    Biochem Biophys Res Commun

    (1991)
  • H. Ali et al.

    Isolation and properties of cardiac and other mast cells from the rat guinea-pig

    Agent Action

    (1985)
  • W.N. Abouhamad et al.

    Peptide transport and chemotaxis in Escherichia coli and Salmonella typhimurium: characterization of the dipeptide permease (Dpp) and the dipeptide binding protein

    Mol Microbiol

    (1991)
  • M. Amellal et al.

    Sodium-potassium ATPase inhibition potentiates compound 48/80-induced histamine secretion from mast cells

    Br J Pharmacol

    (1984)
  • M. Amellal et al.

    Transmembrane sodium and potassium gradients modulate histamine secretion induced by ionophore A23187

    Br J Pharmacol

    (1985)
  • M. Aridor et al.

    Exocytosis in mast cells by basic secretaguogues: evidence for direct activation of GTP-binding proteins

    J Cell Biol

    (1990)
  • K.E. Barrett et al.

    Mast cells isolated from guinea-pig lung: Characterization and studies on histamine secretion

    Agent Action

    (1983)
  • K.E. Barrett et al.

    Mast cell heterogeneity in higher animals. A comparison of the properties of autologous lung and intestinal mast cells from non human primates

    J Immunol

    (1986)
  • R.C. Benyon et al.

    Human skin mast cells: their dispersion, purification and secretory characterization

    J Immunol

    (1987)
  • C. Bronner et al.

    Antigenic and peptidergic pathways of mast cell activation

  • J.L. Bueb et al.

    Activation of Gi-like proteins, a receptor-independent effect of kinins in mast cells

    Mol Pharmacol

    (1990)
  • Cited by (129)

    • Mast cell anaphylatoxin receptor expression can enhance IgE-dependent skin inflammation in mice

      2013, Journal of Allergy and Clinical Immunology
      Citation Excerpt :

      Many studies have reported the expression of C3aR and C5aR on mast cell populations,11,13,35,36 and a blocking antibody against C5aR can reduce C5a-mediated degranulation of human skin mast cells in vitro, which is evidence that C5a can directly activate human skin mast cells through C5aR.11 However, other groups have reported that C3a and C5a, which are cationic, can bind nonspecifically to rat peritoneal mast cells through electrostatic interactions with anionic heparin-proteoglycan on the mast cell surface.37-39 C3a- or C5a-induced ear-swelling responses were significantly reduced in mast cell–engrafted KitW-sh/W-sh mice, the skin mast cells of which lacked C3aR or C5aR, respectively, confirming that the binding of each anaphylatoxin to its specific receptors on skin mast cells can markedly enhance the skin-swelling response induced by that anaphylatoxin in vivo.

    • Relevance of mast cell-nerve interactions in intestinal nociception

      2012, Biochimica et Biophysica Acta - Molecular Basis of Disease
      Citation Excerpt :

      In human, seven Mrg receptors are expressed; MrgX1-MrgX7, while in rodents, the family of Mrg receptors can be further subdivided in MrgD and three subfamilies; MrgA, MrgB and MrgC based on homology analysis [113]. Several ligands such as; BAM peptides, neuropeptide FF (NPFF), dynorphin 14 and γ2-melanocyte-stimulating hormone are capable of activating Mrg-receptors [64,87,90,106,114,116,131,132,139,152,186,221]. Peptides known to activate the MrgC receptor have been shown to elicit pain-like behavior when administrated to rats [82].

    • G protein coupled receptor specificity for C3a and compound 48/80-induced degranulation in human mast cells: Roles of Mas-related genes MrgX1 and MrgX2

      2011, European Journal of Pharmacology
      Citation Excerpt :

      Furthermore, MrgX1 and MrgX2 are expressed in human cord blood-derived mast cells and compound 48/80 activates transfected cells expressing MrgX2 but not MrgX1 (Tatemoto et al., 2006). Previous studies indicated that C3a could activate both human skin mast cells and rat peritoneal mast cells via a pathway similar to that mediated via compound 48/80 (el-Lati et al., 1994; Mousli et al., 1992; 1994). This raises the intriguing possibility that C3a-induced mast cell degranulation could involve both C3a receptor and MrgX2.

    • Mast Cells and Basophils

      2023, Inflammatory Mechanisms in Allergic Diseases
    View all citing articles on Scopus
    View full text