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Protective mechanism of beta-SQAG9 liposome, a sulfonoglycolipid extracted from sea urchin intestines, against hepatic ischemia reperfusion injury.

Abstract
We previously reported that beta-SQAG9 liposome, a sulfonoglycolipid extracted from sea urchin intestines, had a protective effect against hepatic ischemia reperfusion (I/R) injury. In this study, we made a detailed investigation of this protective effect and its mechanism. Rats were pretreated either with beta-SQAG9 liposome (treated group) or with phosphate-buffered saline solution (control group). Thereafter, they were subjected to partial hepatic I/R. The serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were measured, and histological damage was evaluated with hematoxylin and eosin staining. To investigate the protective mechanism of beta-SQAG9 liposome on I/R injury, the serum levels and the tissue messenger RNA levels of TNF-alpha and IL-1beta were measured, and polymorphonuclear neutrophil (PMN) infiltration was histologically evaluated by immunohistochemistry. Moreover, to investigate an interaction between beta-SQAG9 liposome and L-selectin on PMNs, flow cytometric analysis and immunofluorescence were performed. beta-SQAG9 liposome reduced the hepatic I/R injury. The pretreatment with beta-SQAG9 liposome reduced the PMN infiltration into the liver parenchyma. On the other hand, there was no apparent difference in the serum levels and the tissue messenger RNA levels of the proinflammatory cytokines between the two groups. Thus, beta-SQAG9 liposome might reduce the hepatic I/R injury by inhibition of the PMN infiltration into the liver parenchyma, which was independent of the regulation of cytokine production. Moreover, we demonstrated that beta-SQAG9 liposome specifically bound to L-selectin on PMN cell surface, which mediated the PMN infiltration. beta-SQAG9 liposome might competitively antagonize L-selectin on PMNs and suppress the subsequent PMN infiltration, resulting in the reduction in I/R injury.
AuthorsHiroaki Shima, Tetsuhiro Tsuruma, Hiroeki Sahara, Mika Takenouchi, Nobuaki Takahashi, Yuji Iwayama, Atsuhito Yagihashi, Naoki Watanabe, Noriyuki Sato, Koichi Hirata
JournalShock (Augusta, Ga.) (Shock) Vol. 28 Issue 1 Pg. 94-100 (Jul 2007) ISSN: 1073-2322 [Print] United States
PMID17483740 (Publication Type: Journal Article)
Chemical References
  • Glycolipids
  • Interleukin-1beta
  • Liposomes
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • sulfoquinovosylacylglycerol
  • L-Selectin
  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases
  • Alanine Transaminase
Topics
  • Alanine Transaminase (blood)
  • Animals
  • Aspartate Aminotransferases (blood)
  • Glycolipids (administration & dosage, isolation & purification, metabolism, pharmacology)
  • In Vitro Techniques
  • Interleukin-1beta (blood, genetics)
  • L-Lactate Dehydrogenase (blood)
  • L-Selectin (metabolism)
  • Liposomes
  • Liver (blood supply, drug effects, injuries, metabolism)
  • Male
  • Neutrophils (metabolism)
  • RNA, Messenger (genetics, metabolism)
  • Rats
  • Rats, Inbred Lew
  • Reperfusion Injury (genetics, metabolism, pathology, prevention & control)
  • Sea Urchins (chemistry)
  • Tumor Necrosis Factor-alpha (blood, genetics)

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