TY - JOUR
T1 - Neutralization of osteopontin ameliorates acute lung injury induced by intestinal ischemia-reperfusion
AU - Hirano, Yohei
AU - Aziz, Monowar
AU - Yang, Weng Lang
AU - Ochani, Mahendar
AU - Wang, Ping
N1 - Publisher Copyright:
© Copyright 2016 by the Shock Society.
PY - 2016
Y1 - 2016
N2 - Intestinal 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 (25mg/ mouse) or normal IgG isotype control (25mg/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-1b, and MIP-2 was also significantly downregulated in the anti-OPN Abtreated mice as compared with the IgG control mice. Besides, the lungMPOand 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.
AB - Intestinal 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 (25mg/ mouse) or normal IgG isotype control (25mg/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-1b, and MIP-2 was also significantly downregulated in the anti-OPN Abtreated mice as compared with the IgG control mice. Besides, the lungMPOand 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.
KW - Acute Respiratory Distress Syndrome
KW - Infiltration
KW - Inflammation
KW - Intestinal Ischemia-Reperfusion
KW - Neutrophil
KW - Osteopontin
UR - http://www.scopus.com/inward/record.url?scp=84961226943&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84961226943&partnerID=8YFLogxK
U2 - 10.1097/SHK.0000000000000611
DO - 10.1097/SHK.0000000000000611
M3 - Article
C2 - 26974422
AN - SCOPUS:84961226943
SN - 1073-2322
VL - 46
SP - 431
EP - 438
JO - Shock
JF - Shock
IS - 4
ER -