Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury
| Autor: | Hideo Yagita, Yuko Kojima, Takeshi Fukuhara, Kenichi Ikejima, Kazuyoshi Takeda, Hisashi Bashuda, Jiro Kitaura, Kyoko Fukuhara, Ko Okumura, Enzhi Yin, Koichiro Uchida |
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| Rok vydání: | 2021 |
| Předmět: |
Science
medicine.medical_treatment Immunology Ischemia Gene Expression Receptors Cell Surface Pharmacology Protective Agents Article Proinflammatory cytokine Pathogenesis Mice Liver Function Tests Transplant immunology medicine Animals Humans Multidisciplinary biology business.industry Antibodies Monoclonal Immunotherapy medicine.disease Antibodies Anti-Idiotypic Liver Transplantation Disease Models Animal medicine.anatomical_structure Liver Neutrophil Infiltration Reperfusion Injury Hepatocyte Hepatocytes biology.protein Medicine Antibody business Cell Adhesion Molecules Infiltration (medical) Reperfusion injury Signal Transduction |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The prognosis of the liver transplant patients was frequently deteriorated by ischemia and reperfusion injury (IRI) in the liver. Infiltration of inflammatory cells is reported to play critical roles in the pathogenesis of hepatic IRI. Although T lymphocytes, neutrophils and monocytes infiltrated into the liver underwent IRI, we found that neutrophil depletion significantly attenuated the injury and serum liver enzyme levels in a murine model. Interestingly, the expression of CD321/JAM-A/F11R, one of essential molecules for transmigration of circulating leukocytes into inflammatory tissues, was significantly augmented on hepatic sinusoid endothelium at 1 h after ischemia and maintained until 45 min after reperfusion. The intraportal administration of anti-CD321 monoclonal antibody (90G4) significantly inhibited the leukocytes infiltration after reperfusion and diminished the damage responses by hepatic IRI (serum liver enzymes, inflammatory cytokines and hepatocyte cell death). Taken together, presented results demonstrated that blockade of CD321 by 90G4 antibody significantly attenuated hepatic IRI accompanied with substantial inhibition of leukocytes infiltration, particularly inhibition of neutrophil infiltration in the early phase of reperfusion. Thus, our work offers a potent therapeutic target, CD321, for preventing liver IRI. |
| Databáze: | OpenAIRE |
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