Biochemical alteration of membrane-associated IL-6 RI (80-kDa) in adherent macrophages and vascular endothelium

被引:3
作者
Coyne, CP [1 ]
Howell, T
Baravick, J
Baravick, E
Willetto, C
Fenwick, BW
机构
[1] Mississippi State Univ, Coll Vet Med, Vet Pharmacol Res Lab, Vet Res Program, Mississippi State, MS 39762 USA
[2] Kansas State Univ, Coll Vet Med, Dept Pathobiol & Mol Biol, Manhattan, KS 66507 USA
关键词
IL-6 RI (80-kDa); cytokine receptors; shedding events; enzyme-proteases; macrophages; vascular endothelium;
D O I
10.1016/S0161-5890(01)00074-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The potential biochemical mechanisms that mediate the 'shedding' of soluble IL-6 RI (80-kDa) receptor fragments in populations of adherent macrophages were explored. Stimulated macrophages displayed proportional increases in both the expression of membrane-associated IL-6 RI (80-kDa) and the release of soluble receptor fragments. The use of protease inhibitors implicated thiol/cysteine and carboxyl/aspartate proteases in this process. Cathepsin-D depleted membrane-associated IL-6 RI (80-kDa) complexes and generated soluble receptor fragments. A carboxyl/aspartate protease from activated macrophages isolated utilizing pepstatin-A affinity chromatography, was also found to affect membrane-associated IL-6 RI (80-kDa) complexes and generate soluble receptor fragments. Most likely, this fraction corresponded to cathepsin-D based upon its origin, pepstatin-A binding avidity, Hb-PAGE zymography, and hydrolysis of an enzyme-specific substrate. We conclude that cathepsin-D can generate soluble fragments of IL-6 RI (80-kDa) expressed by both macrophages and vascular endothelium. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:347 / 357
页数:11
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