%0 Journal Article
%T Prevention of LPS-Induced Acute Lung Injury in Mice by Progranulin
%A Zhongliang Guo
%A Qinchuan Li
%A Yang Han
%A Yongjie Liang
%A Zengguang Xu
%A Tao Ren
%J Mediators of Inflammation
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/540794
%X The acute respiratory distress syndrome (ARDS), a clinical complication of severe acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. Despite decades of research, few therapeutic strategies for clinical ARDS have emerged. Here we carefully evaluated the effect of progranulin (PGRN) in treatment of ARDS using the murine model of lipopolysaccharide (LPS)-induced ALI. We reported that administration of PGRN maintained the body weight and survival of ALI mice. We revealed that administration of PGRN significantly reduced LPS-induced pulmonary inflammation, as reflected by reductions in total cell and neutrophil counts, proinflammatory cytokines, as well as chemokines in bronchoalveolar lavage (BAL) fluid. Furthermore, administration of PGRN resulted in remarkable reversal of LPS-induced increases in lung permeability as assessed by reductions in total protein, albumin, and IgM in BAL fluid. Consistently, we revealed a significant reduction of histopathology changes of lung in mice received PGRN treatment. Finally, we showed that PGRN/TNFR2 interaction was crucial for the protective effect of PGRN on the LPS-induced ALI. Our findings strongly demonstrated that PGRN could effectively ameliorate the LPS-induced ALI in mice, suggesting a potential application for PGRN-based therapy to treat clinical ARDS. 1. Introduction The acute respiratory distress syndrome (ARDS), a clinically important complication of severe acute lung injury (ALI) in humans, is a significant cause of morbidity and mortality in critically ill patients [1¨C5]. Infectious etiologies, such as sepsis and pneumonia, are leading causes of ALI [1, 2, 5]. Histologically, ALI in humans is characterized by a severe acute inflammatory response in the lungs and neutrophilic alveolitis [1, 5]. The physiological hallmark of ARDS is disruption of the alveolar-capillary membrane barrier, leading to development of noncardiogenic pulmonary edema, in which a proteinaceous exudate floods the alveolar spaces, impairs gas exchange, and precipitates respiratory failure [1, 5¨C7]. ALI can result in persistent respiratory failure and prolonged dependence on mechanical ventilation, increasing susceptibility to multiorgan dysfunction and mortality [8]. Despite extensive investigation aimed at early diagnostic and pathogenetic factors of ALI, current management is mainly supportive, as specific therapies have not been identified [5, 9¨C13]. Animal models focused on ALI pathogenesis have yielded insights into mechanisms that initiate injury; however, little is
%U http://www.hindawi.com/journals/mi/2012/540794/