Monocyte selectivity and tissue localization suggests a role for breast and kidney-expressed chemokine (BRAK) in macrophage development

Although numerous chemokines act on monocytes, none of them is specific for these cells. Here, we show that breast and kidney-expressed chemokine (BRA K) is a highly selective monocyte chemoattractant. Migration efficacy and B ordetella pertussis toxin-sensitive Ca2+ Mobilization responses to BRAK wer e strongly enhanced after treatment of monocytes with the cyclic AMP-elevat ing agents prostaglandin E-2 and forskolin. BRAK is the first monocyte-sele ctive chemokine, as other types of blood leukocytes or monocyte-derived den dritic cells and macrophages did not respond. Expression in normal skin ker atinocytes and dermal fibroblasts as well as lamina propria cells in normal intestinal tissues suggests a homeostatic rather than an inflammatory func tion for this chemokine. In addition, macrophages were frequently found to colocalize with BRAK-producing fibroblasts. We propose that BRAK is involve d in the generation of tissue macrophages by recruiting extravasated precur sors to fibroblasts, which are known to secrete essential cytokines for mac rophage development.