Morales Heidi, Muharemagic Alma, Gantress Jennifer, Cohen Nicholas, Robert Jacques
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Cell Stress Chaperones. 2003 Fall;8(3):265-71. doi: 10.1379/1466-1268(2003)008<0265:bsutse>2.0.co;2.
The presence of the soluble intracellular heat shock protein gp96 (an endoplasmic reticulum resident protein) at the surface of certain cell types is an intriguing phenomenon whose physiological significance has been unclear. We have shown that the active surface expression of gp96 by some immune cells is found throughout the vertebrate phylum including the Agnatha, the only vertebrate taxon whose members (lamprey, hagfish) lack an adaptive immune system. To determine whether gp96 surface expression can be modulated by pathogens, we investigated the effects of in vitro stimulation by purified lipopolysaccharide (LPS) and the heat-killed gram-negative bacteria, Escherichia coli and Aeromonas hydrophilia. Purified Xenopus B cells are readily activated and markedly proliferate in vitro in response to the heat-killed bacteria but not to purified LPS. Furthermore, messenger ribonucleic acid, and intracellular and surface protein expressions of both gp96 and immunoglobulin were upregulated only after activation of B cells by heat-killed bacteria. These data are consistent with an ancestral immunological role of gp96 as an antigen-presenting or danger-signaling molecule, or both, interacting directly with antigen-presenting cells, T cells, or natural killer cells, (or all), to trigger or amplify immune responses.
可溶性细胞内热休克蛋白gp96（一种内质网驻留蛋白）在某些细胞类型表面的存在是一个有趣的现象，其生理意义尚不清楚。我们已经表明，包括无颌类动物（脊椎动物中唯一其成员（七鳃鳗、盲鳗）缺乏适应性免疫系统的分类群）在内的整个脊椎动物门中，一些免疫细胞都会出现gp96的活性表面表达。为了确定gp96的表面表达是否可被病原体调节，我们研究了纯化的脂多糖（LPS）以及热灭活的革兰氏阴性菌大肠杆菌和嗜水气单胞菌的体外刺激作用。纯化的非洲爪蟾B细胞在体外很容易被激活并显著增殖，这是对热灭活细菌的反应，而不是对纯化的LPS的反应。此外，只有在热灭活细菌激活B细胞后，gp96和免疫球蛋白的信使核糖核酸、细胞内和表面蛋白表达才会上调。这些数据与gp96作为抗原呈递或危险信号分子，或两者兼具，直接与抗原呈递细胞、T细胞或自然杀伤细胞（或全部）相互作用以触发或放大免疫反应的原始免疫作用相一致。
