Expression of the chemokine receptor CCR3 on human mast cells

Int Arch Allergy Immunol. Jan-Mar 2001;124(1-3):146-50. doi: 10.1159/000053694.

Abstract

Background: The aim of this study was to investigate whether human mast cells express functional active CCR3 receptors, which are activated by CC chemokines. These ligands include the CCR3-selective chemokines eotaxin and eotaxin-2 and the more promiscuous CC chemokines, MCP-4, MCP-3, MCP-2 and RANTES.

Methods: Immunohistochemical analysis was performed on skin, gut and lung specimens. Double immunostaining was performed with anti-CCR3 and antitryptase, and anti-CCR3 and antichymase antibody (Ab) by using the avidin-biotin-peroxidase system with two different substrates. Mast cells were isolated and purified from human lung parenchyma (HLMC) by countercurrent elutriation followed by discontinuous Percoll density gradient. Flow-cytometric analysis of HLMC surface CCR3 expression was performed with the monoclonal Ab anti-CCR3 (7B11). Functional activation of HLMC was verified by the ability of cells to release histamine and/or migrate in response to eotaxin.

Results: High percentages (>70%) of tryptase-positive cells showing CCR3 expression were found in the skin and in the intestinal submucosa, whereas much lower percentages (< or = 20%) were found in the intestinal mucosa and in the lung interstitium. Eotaxin (1-100 nM) neither induced histamine release from HLMC nor enhanced anti-IgE-induced histamine release. In contrast, eotaxin (10-100 nM) and RANTES (10-100 nM) induced HLMC chemotaxis in vitro. Preincubation of HLMC with antibody anti-CCR3 (5 microg/ml) before loading into the chemotaxis chamber abrogated chemotaxis elicited by eotaxin. Double immunostaining with anti-CCR3 and anti-chymase antibody showed that the vast majority of CCR3-expressing mast cells in the various human tissues examined were tryptase-chymase double-positive.

Conclusions: These results indicate that CCR3 is expressed on human mast cells and that these cells are attracted by CCR3-binding chemokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chemokine CCL11
  • Chemokine CCL5 / pharmacology
  • Chemokines, CC*
  • Chemotaxis
  • Cytokines / pharmacology
  • Humans
  • Intestinal Mucosa / metabolism
  • Lung / cytology
  • Lung / metabolism
  • Mast Cells / drug effects
  • Mast Cells / metabolism*
  • Mast Cells / physiology
  • Receptors, CCR3
  • Receptors, Chemokine / metabolism*
  • Skin / metabolism

Substances

  • CCL11 protein, human
  • CCR3 protein, human
  • Chemokine CCL11
  • Chemokine CCL5
  • Chemokines, CC
  • Cytokines
  • Receptors, CCR3
  • Receptors, Chemokine