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J Appl Physiol 103: 2077-2083, 2007. First published October 4, 2007; doi:10.1152/japplphysiol.00239.2007
8750-7587/07 $8.00
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Bleomycin-induced pulmonary fibrosis is attenuated by a monoclonal antibody targeting HER2

Jihane A. Faress,1,4 David E. Nethery,1 Elizabeth F. O. Kern,2,4 Rosana Eisenberg,3 Frank J. Jacono,1,4 Chris L. Allen,1 and Jeffrey A. Kern1,4

Divisions of 1Pulmonary, Critical Care and Sleep Medicine, and 2Clinical and Molecular Endocrinology, and 3Departments of Internal Medicine and Pathology, University Hospitals Case Medical Center, Case Western Reserve University, and 4Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio

Submitted 28 February 2007 ; accepted in final form 30 September 2007

The importance of HER2/HER3 signaling in decreasing the effects of lung injury was recently demonstrated. Transgenic mice unable to signal through HER2/HER3 had significantly less bleomycin-induced pulmonary fibrosis and showed a survival benefit. Based on these data, we hypothesized that pharmacological blockade of HER2/HER3 in vivo in wild-type mice would have the same beneficial effects. We tested this hypothesis in a bleomycin lung injury model using 2C4, a monoclonal antibody directed against HER2 that blocks HER2/HER3 signaling. The administration of 2C4 before injury decreased the effects of bleomycin at days 15 and 21 after injury. HER2/HER3 blockade resulted in less collagen deposition (362.8 ± 37.9 compared with 610.5 ± 27.1 µg/mg; P = 0.03) and less lung morphological changes (injury score of 1.99 ± 1.55 vs. 3.90 ± 0.76; P < 0.04). In addition, HER2/HER3 blockade resulted in a significant survival advantage with 50% vs. 25% survival at 30 days (P = 0.04). These results confirm that HER2 signaling can be pharmacologically targeted to reduce lung fibrosis and remodeling after injury.

bleomycin lung injury; HER2 blockade


Address for reprint requests and other correspondence: J. A. Faress, Div. of Pulmonary, Critical Care and Sleep Medicine, Dept. of Medicine, Univ. Hospitals Case Medical Center, Case Western Reserve Univ., 11100 Euclid Ave., Wearn 610, Cleveland, OH 44106 (e-mail: jihanefares{at}gmail.com)




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