Endogenous protein and enzyme fragments induce immunoglobulin E-independent activation of mast cells via a G protein-coupled receptor, MRGPRX2

Scand J Immunol. 2018 May;87(5):e12655. doi: 10.1111/sji.12655. Epub 2018 Apr 2.

Abstract

Mast cells play a central role in inflammatory and allergic reactions by releasing inflammatory mediators through 2 main pathways, immunoglobulin E-dependent and E-independent activation. In the latter pathway, mast cells are activated by a diverse range of basic molecules (collectively known as basic secretagogues) through Mas-related G protein-coupled receptors (MRGPRs). In addition to the known basic secretagogues, here, we discovered several endogenous protein and enzyme fragments (such as chaperonin-10 fragment) that act as bioactive peptides and induce immunoglobulin E-independent mast cell activation via MRGPRX2 (previously known as MrgX2), leading to the degranulation of mast cells. We discuss the possibility that MRGPRX2 responds various as-yet-unidentified endogenous ligands that have specific characteristics, and propose that MRGPRX2 plays an important role in regulating inflammatory responses to endogenous harmful stimuli, such as protein breakdown products released from damaged or dying cells.

Keywords: cell activation; cell surface molecules; cells; in vitro; mast cells/basophils; molecules; processes; signal transduction; subject.

MeSH terms

  • Animals
  • Cell Degranulation / immunology*
  • Cell Line, Tumor
  • Chaperonin 10 / immunology
  • HEK293 Cells
  • Humans
  • Immunoglobulin E / immunology*
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology*
  • PC12 Cells
  • Peptide Fragments / immunology*
  • Rats
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / immunology*
  • Receptors, Neuropeptide / genetics
  • Receptors, Neuropeptide / immunology*
  • Swine

Substances

  • Chaperonin 10
  • MRGPRX2 protein, human
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Immunoglobulin E