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Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis
Roderick J. Phillips, … , Michael P. Keane, Robert M. Strieter
Roderick J. Phillips, … , Michael P. Keane, Robert M. Strieter
Published August 1, 2004
Citation Information: J Clin Invest. 2004;114(3):438-446. https://doi.org/10.1172/JCI20997.
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Article Cell biology Article has an altmetric score of 13

Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis

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Abstract

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.

Authors

Roderick J. Phillips, Marie D. Burdick, Kurt Hong, Marin A. Lutz, Lynne A. Murray, Ying Ying Xue, John A. Belperio, Michael P. Keane, Robert M. Strieter

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Figure 5

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Representative histopathology and morphometric analysis of picrosirius r...
Representative histopathology and morphometric analysis of picrosirius red in bleomycin-induced pulmonary fibrosis and expression of α-SMA in the presence of neutralizing anti-CXCL12 or control Ab’s. (A) Representative H&E-stained histopathologic sections of lung tissue on day 16 after intratracheal bleomycin administration in the presence of daily injections of either control (upper panel) or neutralizing anti-CXCL12 Ab’s (lower panel). (B) Morphometric analysis of picrosirius red–stained lung tissue was measured by image analysis (NIH Image 1.55) and expressed as area (square pixels) at ×400 magnification. *P < 0.001. (C) Histopathologic sections of lung tissue on day 16 after intratracheal bleomycin administration in the presence of daily injections of either control (left panel) or neutralizing anti-CXCL12 Ab’s (right panel) stained with α-SMA. Representative fields viewed at ×400 magnification.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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