Neutralization of osteopontin ameliorates acute lung injury induced by intestinal ischemia-reperfusion

Yohei Hirano, Monowar Aziz, Weng Lang Yang, Mahendar Ochani, Ping Wang

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)431-438
Number of pages8
JournalShock
Volume46
Issue number4
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • Acute Respiratory Distress Syndrome
  • Infiltration
  • Inflammation
  • Intestinal Ischemia-Reperfusion
  • Neutrophil
  • Osteopontin

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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