• Yohei Hirano, Monowar Aziz, Weng-Lang Yang, Mahendar Ochani, and Ping Wang.
• *Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, New York †Department of Emergency and Critical Care Medicine, Juntendo University, Urayasu Hospital, Urayasu, Chiba, Japan ‡Department of Surgery, Hofstra Northwell School of Medicine, Manhasset, New York.
• Shock. 2016 Oct 1; 46 (4): 431-8.

AbstractIntestinal ischemia-reperfusion (I/R) is associated with acute respiratory distress syndrome. Osteopontin (OPN), a glycoprotein secreted from immune-reactive cells, plays a deleterious role in various inflammatory diseases. Considering OPN as a pro-inflammatory molecule, we hypothesize that the treatment with its neutralizing antibody (anti-OPN Ab) protects mice against intestinal I/R-induced acute lung injury (ALI). Intestinal I/R was induced in mice by superior mesenteric artery occlusion with a vascular clip. After 45 min of occlusion, the clip was removed and anti-OPN Ab (25 μg/mouse) or normal IgG isotype control (25 μg/mouse) was immediately administrated intravenously. Blood, small intestine, and lung tissues were collected at 4 h after reperfusion for various analyses. After intestinal I/R, mRNA and protein levels of OPN were significantly induced in the small intestine, lungs, and blood relative to sham-operated animals. Compared with the IgG control group, treatment of anti-OPN Ab significantly reduced plasma levels of pro-inflammatory cytokine and chemokine (IL-6 and MIP-2) and organ injury markers (AST, ALT, and LDH). The histological architecture of the gut and lung tissues in anti-OPN Ab-treated intestinal I/R-induced mice showed significant improvement versus the IgG control mice. The lung inflammation measured by the levels of IL-6, IL-1β, and MIP-2 was also significantly downregulated in the anti-OPN Ab-treated mice as compared with the IgG control mice. Besides, the lung MPO and neutrophil infiltration in anti-OPN Ab-treated mice showed significant reduction as compared with the IgG control animals. In conclusion, we have demonstrated beneficial outcomes of anti-OPN Ab treatment in protecting against ALI, implicating a novel therapeutic potential in intestinal I/R.

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