P-selectin glycoprotein ligand 1 deficiency prevents development of acute pancreatitis by attenuating leukocyte infiltration.
P-selectin glycoprotein ligand 1 deficiency prevents development of acute pancreatitis by attenuating leukocyte infiltration.
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P-选择素糖蛋白配体 1 缺陷可通过减弱白细胞浸润来预防急性胰腺炎的发展
DOI：
10.3748/wjg.v26.i41.6361
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发表时间：
2020-11-07
影响因子：
4.3
通讯作者：
Qin T
中科院分区：
文献类型：
--
作者：
Zhang X;Zhu M;Jiang XL;Liu X;Liu X;Liu P;Wu XX;Yang ZW;Qin T
背景：急性胰腺炎（AP）是一种快速发作的胰腺炎症，可引起局部和全身炎症反应综合征（SIRS），发病率和死亡率高，但目前尚无批准的治疗方法。p -选择素糖蛋白配体1 （PSGL-1）是一种启动炎症反应的跨膜糖蛋白。我们推测PSGL-1可能参与了AP的发生发展，可能成为治疗AP的新靶点。目的探讨PSGL-1在AP发生发展中的作用及其机制。方法检测AP患者和志愿者外周血白细胞中PSGL-1的表达。在PSGL-1敲除（psgl -/-）和野生型（psgl - +/+）小鼠诱导的AP小鼠模型中，测量胰腺损伤、炎症细胞因子表达和炎症细胞浸润。在外周血单核细胞(PBMC)-内皮细胞共培养系统中测定白细胞与内皮细胞的粘附。结果AP患者单核细胞和中性粒细胞中PSGL-1的表达明显升高。与PSGL-1+/+小鼠相比，毛蛋白诱导的PSGL-1-/- AP小鼠血清淀粉酶降低，白细胞介素-1 β (il -1 β)和白细胞介素-6 （IL-6）表达减少，中性粒细胞和巨噬细胞浸润减少，外周中性粒细胞和单核细胞数量减少。PSGL-1缺乏通过IL-6而非il -1 β减轻了白细胞与内皮细胞的粘附。结论PSGL-1缺乏可通过刺激IL-6抑制白细胞与内皮细胞的粘附，从而有效抑制AP的发展，可能成为治疗AP的潜在靶点。
BACKGROUND Acute pancreatitis (AP) is rapid-onset pancreatic inflammation that causes local and systemic inflammatory response syndrome (SIRS) with high morbidity and mortality, but no approved therapies are currently available. P-selectin glycoprotein ligand 1 (PSGL-1) is a transmembrane glycoprotein to initiate inflammatory responses. We hypothesized that PSGL-1 may be involved in the development of AP and would be a new target for the treatment of AP. AIM To investigate the role and mechanism of PSGL-1 in the development of AP. METHODS The PSGL-1 expression on leukocytes was detected in peripheral blood of AP patients and volunteers. Pancreatic injury, inflammatory cytokines expression, and inflammatory cell infiltration was measured in AP mouse models induced with PSGL-1 knockout (PSGL-1-/-) and wild-type (PSGL-1+/+) mice. Leukocyte-endothelial cell adhesion was measured in a peripheral blood mononuclear cell (PBMC)-endothelial cell coculture system. RESULTS The expression of PSGL-1 on monocytes and neutrophils was significantly increased in AP patients. Compared with PSGL-1+/+ mice, PSGL-1-/- AP mice induced by caerulein exhibited lower serum amylase, less Interleukin-1beta (IL-1beta) and Interleukin-6 (IL-6) expression, less neutrophil and macrophage infiltration, and reduced peripheral neutrophil and monocyte accounts. PSGL-1 deficiency alleviated leukocyte-endothelial cell adhesion via IL-6 but not IL-1beta. CONCLUSION PSGL-1 deficiency effectively inhibits the development of AP by preventing leukocyte-endothelial cell adhesion via IL-6 stimulation and may become a potential therapeutic target for treating AP.
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影响因子：
29.4
作者：
Gukovskaya AS;Gukovsky I;Algül H;Habtezion A
通讯作者：
Habtezion A
影响因子：
4.8
作者：
Aleisa，Fajr A.;Sakashita，Kosuke;Merzaban，Jasmeen S.
通讯作者：
Merzaban，Jasmeen S.
影响因子：
46.9
作者：
Fischer, M;Goldschmitt, J;RoseJohn, S
通讯作者：
RoseJohn, S
影响因子：
20.3
作者：
Yago, Tadayuki;Liu, Zhenghui;McEver, Rodger P.
通讯作者：
McEver, Rodger P.
影响因子：
16.6
作者：
Geisz A;Sahin-Tóth M
通讯作者：
Sahin-Tóth M