title: CCR2-mediated recruitment of fibrocytes to the alveolar space after fibrotic injury.
abstract: Bone marrow-derived cells are known to play important roles in repair/regeneration of injured tissues, but their roles in pathological fibrosis are less clear. Here, we report a critical role for the chemokine receptor CCR2 in the recruitment and activation of lung fibrocytes (CD45(+), CD13(+), collagen 1(+), CD34(-)). Lung fibrocytes were isolated in significantly greater numbers from airspaces of fluorescein isothiocyanate-injured CCR2(+/+) mice than from CCR2(-/-) mice. Transplant of CCR2(+/+) bone marrow into CCR2(-/-) recipients restored recruitment of lung fibrocytes and susceptibility to fibrosis. Ex vivo PKH-26-labeled CCR2(+/+) lung fibrocytes also migrated to injured airspaces of CCR2(-/-) recipients in vivo. Isolated lung fibrocytes expressed CCR2 and migrated to CCL2, and CCL2 stimulated collagen secretion by lung fibrocytes. Fibrocytes could transition into fibroblasts in vitro, and this transition was associated with loss of CCR2 expression and enhanced production of collagen 1. This is the first report describing expression of CCR2 on lung fibrocytes and demonstrating that CCR2 regulates both recruitment and activation of these cells after respiratory injury.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0642, USA. bmoore@umich.edu
authors.forename: Bethany B
authors.initials: BB
authors.lastname: Moore
authors.forename: Jill E
authors.initials: JE
authors.lastname: Kolodsick
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Thannickal
authors.forename: Kenneth
authors.initials: K
authors.lastname: Cooke
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Moore
authors.forename: Cory
authors.initials: C
authors.lastname: Hogaboam
authors.forename: Carol A
authors.initials: CA
authors.lastname: Wilke
authors.forename: Galen B
authors.initials: GB
authors.lastname: Toews
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D018893:Bronchoalveolar Lavage; D018826:CD13 Antigens / Q000096:biosynthesis; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D002633:Chemotaxis; D003094:Collagen / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005355:Fibrosis; D005434:Flow Cytometry; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: C515335:Ccr2 protein, mouse; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen; D017493:Leukocyte Common Antigens; D018826:CD13 Antigens; D010100:Oxygen
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