Abstract 3308: Enhanced expression of galectin-3 isassociated with the alternative activation of macrophages and development oflung fibrosis following radiation

Abstract

Abstract Radiotherapy is a major treatment approach to non-operable lung cancer patients. Unfortunately, radiation-induced lung injury occurs in 5-20% of lung cancer patients following radiotherapy. Radiation-induced lung fibrosis contributes to an increased risk of death or a decreased quality of life. The mechanism(s) for the development of radiation-induced lung fibrosis is not fully understood, and no interventions to prevent/ameliorate it have proven successful. Macrophages are the first line of defense for airways and alveolar surfaces and play a key role in the initiation and orchestration of inflammatory responses. Two distinct macrophage subsets have been identified; classically activated macrophages (M1) and alternatively activated macrophages (M2). Increased numbers of activated M2 macrophages have been seen in human fibrotic conditions and rodent models of fibrosis. However, the mechanism(s) driving the persistent activation of M2 macrophages and how this leads to the development of fibrosis remains undefined. Recent studies indicate that galectin-3 (gal-3) is potentially a key regulator of M2 macrophage activation; inhibition of gal-3 expression prevents M2 macrophage activation. In this paper, we show elevated numbers of Ym-1 positive alveolar macrophages in the irradiated lung. Increased expression of gal-3 cells was found in the fibrotic lung, which was associated with fibrotic lesions. M2 macrophages were the majority of cells that expressed gal-3. In our in vitro studies, we found that knocking-down gal-3 using Mission lentiviral transduction particles prevented radiation-induced increases in the expression of YM-1 in Raw 264.7 macrophage. Mouse recombinant gal-3 stimulated mouse lung fibroblast cell proliferation and expression of α-SMA. These data suggest that gal-3 appears to regulate alternative activation of M2 macrophage and play an important role in the development of radiation-induced lung injury. Citation Format: Weiling Zhao, Jing-Hua Zhang, Ingrid J. Lopes. Enhanced expression of galectin-3 isassociated with the alternative activation of macrophages and development oflung fibrosis following radiation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3308. doi:10.1158/1538-7445.AM2015-3308