Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury.
Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury.
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DOI：
10.1038/s41598-021-85001-2
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发表时间：
2021-03-18
影响因子：
4.6
通讯作者：
Uchida K
中科院分区：
文献类型：
--
作者：
Yin E;Fukuhara T;Takeda K;Kojima Y;Fukuhara K;Ikejima K;Bashuda H;Kitaura J;Yagita H;Okumura K;Uchida K
肝脏缺血再灌注损伤（IRI）是影响肝移植患者预后的重要因素。据报道，炎症细胞的浸润在肝脏IRI的发病机制中起关键作用。虽然T淋巴细胞，中性粒细胞和单核细胞浸润到肝脏进行IRI，我们发现，中性粒细胞耗竭显着衰减的损伤和血清肝酶水平在小鼠模型。有趣的是，CD 321/JAM-A/F11 R，循环白细胞迁移到炎症组织中的必需分子之一，在缺血后1小时在肝窦内皮上显著增加，并维持至再灌注后45分钟。门静脉注射抗CD 321单克隆抗体（90 G4）可显著抑制再灌注后白细胞浸润，减轻肝脏IRI引起的肝损伤反应（血清肝酶、炎性细胞因子和肝细胞死亡）。综上所述，所呈现的结果表明，通过90 G4抗体阻断CD 321显著减弱肝脏IRI，同时显著抑制白细胞浸润，特别是在再灌注早期抑制中性粒细胞浸润。因此，我们的工作提供了一个有效的治疗靶点，CD 321，用于预防肝脏IRI。
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.
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影响因子：
3.7
作者：
Fukuhara T;Kim J;Hokaiwado S;Nawa M;Okamoto H;Kogiso T;Watabe T;Hattori N
通讯作者：
Hattori N
影响因子：
5.4
作者：
Liu ML;Nagai T;Tokunaga M;Iwanaga K;Matsuura K;Takahashi T;Kanda M;Kondo N;Naito AT;Komuro I;Kobayashi Y
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Kobayashi Y
影响因子：
5.5
作者：
Nourshargh, Sussan;Krombach, Fritz;Dejana, Elisabetta
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Dejana, Elisabetta
影响因子：
30.5
作者：
Kelly, JM;Darcy, PK;Smyth, MJ
通讯作者：
Smyth, MJ
影响因子：
3.2
作者：
Hintermann, Edith;Bayer, Monika;Christen, Urs
通讯作者：
Christen, Urs