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(American Journal of Pathology. 2005;166:675-684.)
© 2005 American Society for Investigative Pathology

CCR2-Mediated Recruitment of Fibrocytes to the Alveolar Space after Fibrotic Injury

Bethany B. Moore*, Jill E. Kolodsick*, Victor J. Thannickal*, Kenneth Cooke{dagger}, Thomas A. Moore*, Cory Hogaboam{ddagger}, Carol A. Wilke* and Galen B. Toews*

From the Department of Internal Medicine,* Pulmonary and Critical Care Medicine Division; the Department of Pediatrics,{dagger} Bone Marrow Transplantation Division; and the Department of Pathology,{ddagger} University of Michigan Medical School, Ann Arbor, Michigan

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.




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