H4 histamine receptor mediates optimal migration of mast cell precursors to CXCL12

J Allergy Clin Immunol. 2007 Oct;120(4):827-34. doi: 10.1016/j.jaci.2007.05.046. Epub 2007 Aug 6.

Abstract

Background: CXCL12, a constitutive chemokine (ligand of CXCR4 and CXCR7), is expressed in the skin and airway epithelium and plays a significant role in allergic airway diseases. The pleiotropic effects of CXCL12 are enhanced by cofactors specific to the target cell.

Objective: We hypothesized that histamine, a major mediator of allergic reactions, could interact with CXCL12 to promote human mast cell (MC) migration.

Methods: The chemotactic effects of CXCL12 alone or in combination with histamine were evaluated on human precursor and mature MCs by using in vitro migration assays.

Results: CXCL12 exerts a chemotactic activity on both precursor and fully mature MCs. Histamine and supernatants from IgE-activated MCs enhanced CXCL12 chemotactic activity on the precursor MC population. The synergy between histamine and CXCL12 was not observed with mature MCs, CD4(+) T cells, and monocytes. Inhibition of histamine receptors pharmacologically or with specific small interfering RNA (siRNA) indicated that synergy between histamine and CXCL12 required the H(4) receptor.

Conclusion: Histamine released by allergen-activated mature MCs might promote MC-rich allergic inflammation by enhancing recruitment of their precursors in tissues constitutively expressing CXCL12, including skin and airways.

Clinical implications: This work highlights a novel role of the H(4) receptor in the perpetuation of allergic responses and provides evidence for the utility of H(4) receptor antagonists in the treatment of allergic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Movement
  • Chemokine CXCL12
  • Chemokines, CXC / physiology*
  • Histamine / pharmacology
  • Histamine Release
  • Humans
  • Mast Cells / physiology*
  • Monocytes / physiology
  • Receptors, CXCR4 / physiology
  • Receptors, G-Protein-Coupled / physiology*
  • Receptors, Histamine / physiology*
  • Receptors, Histamine H4
  • Stem Cells / physiology*

Substances

  • Actins
  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • HRH4 protein, human
  • Receptors, CXCR4
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H4
  • Histamine