title: Monocyte selectivity and tissue localization suggests a role for breast and kidney-expressed chemokine (BRAK) in macrophage development.
abstract: 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 Ca(2+) mobilization responses to BRAK were strongly enhanced after treatment of monocytes with the cyclic AMP-elevating agents prostaglandin E(2) 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.
authors.affiliation: Theodor-Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Kurth
authors.forename: K
authors.initials: K
authors.lastname: Willimann
authors.forename: P
authors.initials: P
authors.lastname: Schaerli
authors.forename: T
authors.initials: T
authors.lastname: Hunziker
authors.forename: I
authors.initials: I
authors.lastname: Clark-Lewis
authors.forename: B
authors.initials: B
authors.lastname: Moser
mesh_terms: D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000235:genetics / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008264:Macrophages / Q000166:cytology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D037342:Pertussis Toxin; D019707:Receptors, Chemokine / Q000378:metabolism; D015398:Signal Transduction; D014018:Tissue Distribution; D010566:Virulence Factors, Bordetella / Q000378:metabolism / Q000494:pharmacology
chemical_list: C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D019707:Receptors, Chemokine; D010566:Virulence Factors, Bordetella; D000242:Cyclic AMP; D037342:Pertussis Toxin