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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 1

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Characterization of human fibrocytes and their trafficking to bleomycin-...
Characterization of human fibrocytes and their trafficking to bleomycin-induced lung fibrosis in SCID mice. (A) Human fibrocytes stained with control Ab, human Col I, human CXCR4, and human α-SMA 3 weeks after purification. Representative fields viewed at ×400 magnification. (B) Isolated human fibrocytes triple-stained for Col I, CD45, and CXCR4 were examined by FACS analysis. Data shows CD45+ fibrocytes that were examined for dual expression of CXCR4 and Col I. (C) Isolated human fibrocyte chemotaxis in response to 0, 30, and 100 ng/ml of CXCL12. Data are representative of three experiments. *P < 0.05. h.p.f., high-powered field. (D) Isolated human fibrocytes (106) were injected into the tail vein of SCID mice at day 4 after treatment with either intratracheal bleomycin (Bleo) or saline, followed by recovery of cells from the lungs at day 8. Cells were then stained for human CD45, Col I, and CXCR4 and analyzed by flow cytometry to determine trafficking of human fibrocytes to the lungs of SCID mice. *P < 0.05.

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

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