The Journal of Experimental Medicine
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Published online 17 September 2001. doi:10.1084/jem.194.6.855
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© The Rockefeller University Press, 0022-1007/2001/9/855/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 6, September 17, 2001 855-862

Brief Definitive Report

Monocyte Selectivity and Tissue Localization Suggests a Role for Breast and Kidney–expressed Chemokine (BRAK) in Macrophage Development

Isabel Kurtha, Katharina Willimanna, Patrick Schaerlia, Thomas Hunzikerb, Ian Clark-Lewisc, and Bernhard Mosera
a Theodor-Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
b Department of Dermatology, University Hospital, CH-3000 Bern, Switzerland
c Biomedical Research Center, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada

Correspondence to: Bernhard Moser, Theodor-Kocher Institute, University of Bern, P.O. Box 99, CH-3000 Bern 9, Switzerland. Tel:41-31-631-4157 Fax:41-31-631-3799 E-mail:bernhard.moser{at}tki.unibe.ch.

Although numerous chemokines act on monocytes, none of them is specific for these cells. Here, we show that breast and kidney–expressed chemokine (BRAK) is a highly selective monocyte chemoattractant. Migration efficacy and Bordetella pertussis toxin–sensitive Ca2+ mobilization responses to BRAK were strongly enhanced after treatment of monocytes with the cyclic AMP–elevating agents prostaglandin E2 and forskolin. BRAK is the first monocyte-selective chemokine, as other types of blood leukocytes or monocyte-derived dendritic cells and macrophages did not respond. Expression in normal skin keratinocytes and dermal fibroblasts as well as lamina propria cells in normal intestinal tissues suggests a homeostatic rather than an inflammatory function for this chemokine. In addition, macrophages were frequently found to colocalize with BRAK-producing fibroblasts. We propose that BRAK is involved in the generation of tissue macrophages by recruiting extravasated precursors to fibroblasts, which are known to secrete essential cytokines for macrophage development.

Key Words: epithelial tissues, chemokine, prostaglandin E2, monocytes, migration


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