[Circulating fibrocytes contribute to the pathogenesis of pulmonary fibrosis]
>>J. Clin. Invest. 114:438-446 (2004)
Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis
Roderick J. Phillips1, Marie D. Burdick1, Kurt Hong2, Marin A. Lutz1, Lynne A. Murray1, Ying Ying Xue1, John A. Belperio1, Michael P. Keane1 and Robert M. Strieter1,3
1Division of Pulmonary and Critical Care Medicine,
2Division of Nutrition, and
3Departments of Pathology and Pediatrics, David Geffen School of Medicine at University of California–Los Angeles, Los Angeles, California, USA.
Address correspondence to: Robert M. Strieter, Division of Pulmonary and Critical Care Medicine, Departments of Medicine, Pathology, and Laboratory Medicine, University of California – Los Angeles, School of Medicine, 900 Veteran Avenue, 14-154 Warren Hall, Los Angeles, California 90095-1786, USA. Phone: (310) 794-1999; Fax: (310) 794-1998; E-mail: rstrieter@mednet.ucla.edu.
Received for publication January 7, 2004, and accepted in revised form June 15, 2004.
Previous reports have identified a circulating pool of CD45+ collagen I+ CXCR4+ (CD45+Col I+CXCR4+) cells, termed fibrocytes, that traffic to areas of fibrosis. No studies have demonstrated that these cells actually contribute to fibrosis, however. Pulmonary fibrosis was originally thought to be mediated solely by resident lung fibroblasts. Here we show that a population of human CD45+Col I+CXCR4+ circulating fibrocytes migrates in response to CXCL12 and traffics to the lungs in a murine model of bleomycin-induced pulmonary fibrosis. Next, we demonstrated that murine CD45+Col I+CXCR4+ fibrocytes also traffic to the lungs in response to a bleomycin challenge. Maximal intrapulmonary recruitment of CD45+Col I+CXCR4+ fibrocytes directly correlated with increased collagen deposition in the lungs. Treatment of bleomycin-exposed animals with specific neutralizing anti-CXCL12 Ab’s inhibited intrapulmonary recruitment of CD45+Col I+CXCR4+ circulating fibrocytes and attenuated lung fibrosis. Thus, our results demonstrate, we believe for the first time, that circulating fibrocytes contribute to the pathogenesis of pulmonary fibrosis.<< |
