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Published online before print January 26, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0904511

Received for publication September 13, 2004.
Revised December 10, 2004.
Accepted for publication December 23, 2004.

Article

Differential expression of CCR3 and CXCR3 by human lung and bone marrow-derived mast cells: implications for tissue mast cell migration

Christopher E. Brightling ^*@, Davinder Kaur ^*, Patrick Berger , Angela J. Morgan ^*, Andrew J. Wardlaw ^*, and Peter Bradding ^*

*Institute for Lung Health, Department of Infection, Immunity and Inflammation, Leicester-Warwick Medical School and University Hospitals of Leicester, United Kingdom; and Laboratoire de Physiologie Cellulaire Respiratoire, INSERM E356, University Victor Segalen Bordeaux 2, France

^@ To whom correspondence should be addressed. E-mail: ceb17{at}le.ac.uk.

	Abstract

The selective microlocalization of mast cells within specific airway structures, such as the airway smooth muscle and submucosal glands, in asthma is important in the pathophysiology of inflammatory lung disease. Chemokines are likely candidates mediating mast cell migration into these tissue compartments. In this study, we have defined the chemokine receptor profile of human lung mast cells (HLMC) compared with mast cells derived from human bone marrow (BM) and the HMC-1. CXC chemokine receptor 3 (CXCR3) was the most highly expressed chemokine receptor on ex vivo HLMC analyzed by flow cytometry, and CXCR3 expression by mast cells in the bronchial mucosa was confirmed by immuno-histochemistry. CXCR3 was functional, inducing a rise in cytosolic-free Ca²⁺, actin reorganization, and chemotaxis in response to the CXC ligands CXCL9, -10, and -11. CXCR3 activation did not induce degranulation or cytokine synthesis. In addition, more than 10% of ex vivo HLMC expressed CC chemokine receptor 3, CXCR1, and CXCR4. It is interesting that CXCR3 was not expressed by human BM-derived mast cells, suggesting its expression is induced during tissue maturation. As CXCR3 ligands are elevated in many pulmonary diseases, CXCR3 may be important for determining the anatomical microlocalization of mast cells within the human lung.

Key Words: chemokine receptors • CXCL10

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