title: Fibrocytes develop outside the kidney but contribute to renal fibrosis in a mouse model.
abstract: Collagen-producing bone marrow-derived cells (fibrocytes) have been detected in animal models and patients with fibrotic diseases. In vitro data suggest that they develop from monocytes with the help of accessory cells and profibrotic soluble factors. Using a mouse model of renal fibrosis, unilateral ureteral obstruction, we found the number of circulating fibrocytes was not reduced when monocytes were depleted with a monoclonal antibody against CCR2 or when CCR2-/- mice with very low numbers of circulating or splenic monocytes were analyzed. The absence of CCR2, however, interfered with migration of fibrocytes into the kidney. The phenotype of splenic and renal fibrocytes was very similar and distinct from classical monocytes as fibrocytes expressed no CD115, medium levels of CCR2, and high levels of CD11b and Ly-6G. Using a depleting monoclonal antibody against Ly-6G or bone marrow chimeric mice expressing the diphtheria toxin receptor under the control of CD11b, we could efficiently deplete fibrocytes from the kidney. Depletion of fibrocytes or reduced migration of fibrocytes into the kidney resulted in lower renal expression of collagen-I. Thus, fibrocytes develop outside the kidney independent of infiltrating monocytes and rely on CCR2 for migration into target organs.
authors.affiliation: Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Reich
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schmidbauer
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez Gomez
authors.forename: Fabian
authors.initials: F
authors.lastname: Johannes Hermann
authors.forename: Nicole
authors.initials: N
authors.lastname: Göbel
authors.forename: Hilke
authors.initials: H
authors.lastname: Brühl
authors.forename: Isabel
authors.initials: I
authors.lastname: Ketelsen
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Talke
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002633:Chemotaxis; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics; D013997:Time Factors; D014517:Ureteral Obstruction / Q000150:complications
chemical_list: D000950:Antigens, Ly; D015415:Biomarkers; D039481:CD11b Antigen; C515335:Ccr2 protein, mouse; C480309:Ly6G antigen, mouse; D054390:Receptors, CCR2; D003094:Collagen