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α2-巨球蛋白信号受体在抗原刺激下的可诱导表达:第二信使生成的研究

Inducible expression of the alpha2-macroglobulin signaling receptor in response to antigenic stimulation: a study of second messenger generation.

作者信息

Bhattacharjee G, Misra U K, Gawdi G, Cianciolo G, Pizzo S V

机构信息

Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.

出版信息

J Cell Biochem. 2001;82(2):260-70. doi: 10.1002/jcb.1152.

DOI:10.1002/jcb.1152
PMID:11527151
Abstract

Thioglycollate (TG)-elicited murine, peritoneal macrophages express two receptors for activated forms of the proteinase inhibitor alpha2-macroglobulin (alpha2M*)--namely, the low density lipoprotein receptor-related protein (LRP) and the alpha2M signaling receptor (alpha2MSR). We now report that resident peritoneal macrophages express only 400+/-50 alpha2MSR receptors/cell compared to 5000+/-500 receptor/TG-elicited macrophage. By contrast, LRP expression is only 2-2.5-fold greater on elicited cells. The low level of alpha2MSR expression by resident cells is insufficient to trigger signal transduction in contrast to TG-elicited cells which when exposed to alpha2M* demonstrate a rapid rise in inositol 1,4,5-trisphosphate and a concomitant increase in cytosolic free Ca2+. We then studied a variety of preparations injected subcutaneously for their ability to upregulate alpha2MSR. Macroaggregated bovine serum albumin (macroBSA) injection upregulated alpha2MSR and triggered signaling responses by splenic macrophages. Nonaggregated BSA injection alone or in the presence of alum, by contrast, did not alter alpha2MSR expression. Recombivax (hepatitis B antigen adsorbed to alum) injection also upregulated alpha2MSR on splenic macrophages while the alum carrier had no effect. We conclude that macrophage alpha2M* receptors are inducible and their expression may be regulated, in part, by potential antigens.

摘要

巯基乙酸盐(TG)诱导的小鼠腹腔巨噬细胞表达两种蛋白酶抑制剂α2-巨球蛋白(α2M*)活化形式的受体,即低密度脂蛋白受体相关蛋白(LRP)和α2M信号受体(α2MSR)。我们现在报告,与5000±500个受体/TG诱导的巨噬细胞相比,驻留腹腔巨噬细胞每个细胞仅表达400±50个α2MSR受体。相比之下,LRP在诱导细胞上的表达仅高2 - 2.5倍。与TG诱导的细胞相反,驻留细胞中α2MSR的低表达水平不足以触发信号转导,TG诱导的细胞在暴露于α2M时,肌醇1,4,5 - 三磷酸迅速升高,胞质游离Ca2+随之增加。然后,我们研究了多种皮下注射制剂上调α2MSR的能力。注射大颗粒牛血清白蛋白(macroBSA)可上调α2MSR,并触发脾巨噬细胞的信号反应。相比之下,单独注射非聚集BSA或在存在明矾的情况下注射,均未改变α2MSR的表达。重组乙肝疫苗(吸附于明矾的乙肝抗原)注射也上调了脾巨噬细胞上的α2MSR,而明矾载体则无作用。我们得出结论,巨噬细胞α2M受体是可诱导的,其表达可能部分受潜在抗原的调节。

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