The Journal of Experimental Medicine
Symposium on Dendritic Cells
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Published online 13 June 2005 doi:10.1084/jem.20042407
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 12, 1961-1971
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ARTICLE

 Leukotriene B4, an activation product of mast cells, is a chemoattractant for their progenitors

Charlotte L. Weller1, Sarah J. Collington1, Jeremy K. Brown2, Hugh R.P. Miller2, Adam Al-Kashi1, Peter Clark1, Peter J. Jose1, Adele Hartnell1, and Timothy J. Williams1

1 Leukocyte Biology Section, Biomedical Sciences Division, Faculty of Medicine, Imperial College London, South Kensington, London SW7 2AZ, England, UK
2 Department of Veterinary Clinical Studies, University of Edinburgh, Easter Bush Veterinary Centre, Roslin, Midlothian, EH25 9RG, Scotland, UK

CORRESPONDENCE Timothy J. Williams: tim.williams{at}imperial.ac.uk

Mast cells are tissue-resident cells with important functions in allergy and inflammation. Pluripotential hematopoietic stem cells in the bone marrow give rise to committed mast cell progenitors that transit via the blood to tissues throughout the body, where they mature. Knowledge is limited about the factors that release mast cell progenitors from the bone marrow or recruit them to remote tissues. Mouse femoral bone marrow cells were cultured with IL-3 for 2 wk and a range of chemotactic agents were tested on the c-kit+ population. Cells were remarkably refractory and no chemotaxis was induced by any chemokines tested. However, supernatants from activated mature mast cells induced pronounced chemotaxis, with the active principle identified as leukotriene (LT) B4. Other activation products were inactive. LTB4 was highly chemotactic for 2-wk-old cells, but not mature cells, correlating with a loss of mRNA for the LTB4 receptor, BLT1. Immature cells also accumulated in vivo in response to intradermally injected LTB4. Furthermore, LTB4 was highly potent in attracting mast cell progenitors from freshly isolated bone marrow cell suspensions. Finally, LTB4 was a potent chemoattractant for human cord blood–derived immature, but not mature, mast cells. These results suggest an autocrine role for LTB4 in regulating tissue mast cell numbers.

Abbreviations used: 5-LO, 5-lipoxygenase; ACN, acetonitrile; BMMC, BM-derived mast cell; CBMC, cord blood– derived mast cell; CMFDA, 5-chloromethylfluorescein diacetate; HSA, human serum albumin; i.d., intradermal; LT, leukotriene; mMCP, murine mast cell protease; SCF, stem cell factor.

A. Hartnell and T. Williams contributed equally to this work.


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