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斑马鱼肝脏凝集素可结合多种细菌,并参与免疫防御。

The hepatic lectin of zebrafish binds a wide range of bacteria and participates in immune defense.

机构信息

Laboratory for Evolution & Development, Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China; Department of Marine Biology, Ocean University of China, Qingdao 266003, China.

Laboratory for Evolution & Development, Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China; Department of Marine Biology, Ocean University of China, Qingdao 266003, China.

出版信息

Fish Shellfish Immunol. 2018 Nov;82:267-278. doi: 10.1016/j.fsi.2018.08.012. Epub 2018 Aug 16.

DOI:10.1016/j.fsi.2018.08.012
PMID:30120977
Abstract

C-type lectins (CTLs) have a diverse range of functions including cell-cell adhesion, immune response to pathogens and apoptosis. Asialoglycoprotein receptor (ASGPR), also known as hepatic lectin, a member of CTLs, was the first animal lectin identified, yet information regarding it remains rather limited in teleost. In this study, we identified a putative protein in zebrafish, named as the zebrafish hepatic lectin (Zhl). The zhl encoded a typical Ca-dependent carbohydrate-binding protein, and was mainly expressed in the liver in a tissue specific fashion. Challenge with LPS and LTA resulted in significant up-regulation of zhl expression, suggesting involvement in immune response. Actually, recombinant C-type lectin domain (rCTLD) of Zhl was found to be capable of agglutinating and binding to both Gram-negative and Gram-positive bacteria and enhancing the phagocytosis of the bacteria by macrophages. Moreover, rCTLD specifically bound to insoluble lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PGN), which were inhibited by galactose. Interestingly, Zhl was located in the membrane, and its overexpression could inhibit the production of pre-inflammatory cytokines. Taken together, these results indicate that Zhl has immune activity capable of defending invading pathogens, enriching our understanding of the function of ASGPR/hepatic lectin.

摘要

C 型凝集素(CTLs)具有多种功能,包括细胞间黏附、对病原体的免疫反应和细胞凋亡。唾液酸糖蛋白受体(ASGPR),也称为肝凝集素,是 CTLs 的成员之一,是第一个被鉴定的动物凝集素,但在硬骨鱼中关于它的信息仍然相当有限。在这项研究中,我们在斑马鱼中鉴定出一种假定的蛋白质,命名为斑马鱼肝凝集素(Zhl)。Zhl 编码了一种典型的 Ca 依赖性碳水化合物结合蛋白,主要在肝脏中以组织特异性的方式表达。LPS 和 LTA 的刺激导致 zhl 表达显著上调,表明其参与免疫反应。实际上,发现 Zhl 的重组 C 型凝集素结构域(rCTLD)能够凝集和结合革兰氏阴性和革兰氏阳性细菌,并增强巨噬细胞对细菌的吞噬作用。此外,rCTLD 特异性结合不溶性脂多糖(LPS)、脂磷壁酸(LTA)和肽聚糖(PGN),这些结合被半乳糖抑制。有趣的是,Zhl 位于膜上,其过表达可以抑制前炎症细胞因子的产生。综上所述,这些结果表明 Zhl 具有防御入侵病原体的免疫活性,丰富了我们对 ASGPR/肝凝集素功能的理解。

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