Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury

Abstract 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 infil...

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Autores principales:	Enzhi Yin, Takeshi Fukuhara, Kazuyoshi Takeda, Yuko Kojima, Kyoko Fukuhara, Kenichi Ikejima, Hisashi Bashuda, Jiro Kitaura, Hideo Yagita, Ko Okumura, Koichiro Uchida
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/da75a8a7537b4d3791b95e3244b60239
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spelling	oai:doaj.org-article:da75a8a7537b4d3791b95e3244b602392021-12-02T17:05:46ZAnti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury10.1038/s41598-021-85001-22045-2322https://doaj.org/article/da75a8a7537b4d3791b95e3244b602392021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85001-2https://doaj.org/toc/2045-2322Abstract 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.Enzhi YinTakeshi FukuharaKazuyoshi TakedaYuko KojimaKyoko FukuharaKenichi IkejimaHisashi BashudaJiro KitauraHideo YagitaKo OkumuraKoichiro UchidaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Enzhi Yin Takeshi Fukuhara Kazuyoshi Takeda Yuko Kojima Kyoko Fukuhara Kenichi Ikejima Hisashi Bashuda Jiro Kitaura Hideo Yagita Ko Okumura Koichiro Uchida Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury
description	Abstract 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.
format	article
author	Enzhi Yin Takeshi Fukuhara Kazuyoshi Takeda Yuko Kojima Kyoko Fukuhara Kenichi Ikejima Hisashi Bashuda Jiro Kitaura Hideo Yagita Ko Okumura Koichiro Uchida
author_facet	Enzhi Yin Takeshi Fukuhara Kazuyoshi Takeda Yuko Kojima Kyoko Fukuhara Kenichi Ikejima Hisashi Bashuda Jiro Kitaura Hideo Yagita Ko Okumura Koichiro Uchida
author_sort	Enzhi Yin
title	Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury
title_short	Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury
title_full	Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury
title_fullStr	Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury
title_full_unstemmed	Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury
title_sort	anti-cd321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/da75a8a7537b4d3791b95e3244b60239
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Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury

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