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J Appl Physiol (October 4, 2007). doi:10.1152/japplphysiol.00239.2007
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Submitted on February 28, 2007
Accepted on September 30, 2007

Bleomycin Induced Pulmonary Fibrosis is Attenuated by a Monoclonal Antibody Targeting HER2

Jihane Abdlemassih Faress1*, David E. Nethery2, Elizabeth F.O. Kern3, Rosana Eisenberg4, Frank J. Jacono3, Chris L. Allen3, and Jeffrey A. Kern3

1 Medicine, Case Western Reserve University, Cleveland , Ohio, United States; Medicine , Case Western Reserve University, 11100 Euclid Avenue , Cleveland , Ohio, 44106-5067, United States
2 Medicine, Case Western Reserve University, Cleveland, Ohio, United States
3 Medicine, Case Western Reserve University, Cleveland , Ohio, United States
4 Pathology, Case Western Reserve University, Cleveland , Ohio, United States

* To whom correspondence should be addressed. E-mail: jihanefares{at}gmail.com.

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 prior to 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 to 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.




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