ENZYMATIC DEGRADATION OF ENDOTHELIN-1 BY ACTIVATED HUMAN POLYMORPHONUCLEAR NEUTROPHILS

被引:12
作者
FAGNY, C
MICHEL, A
NORTIER, J
DESCHODTLANCKMAN, M
机构
[1] UNIV LIBRE BRUXELLES,FAC MED,PLUIRIDISCIPLINAIRE RECH EXPTL BIOMED LAB,BAT EG,CP 603,B-1070 BRUSSELS,BELGIUM
[2] UNIV MONS,FAC SCI,CHIM BIOL LAB,B-7000 MONS,BELGIUM
关键词
ENDOTHELIN-1; LEUKOCYTE ENZYME; CATHEPSIN-G; ENDOPEPTIDASE; 24.11;
D O I
10.1016/0167-0115(92)90021-L
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Endothelin-1 (ET-1)is a potent vasoconstrictor peptide secreted by endothelial cells. We investigated whether polymorphonuclear neutrophils (PMN) were able to destroy this peptide by enzymatic hydrolysis produced either by the membrane-bound endopeptidase 24.11 or by lysosomal proteinases released in the medium by activated cells. Resting and activated PMN were incubated with I-125-labelled ET-1 and the degradation fragments were analyzed by HPLC. A marked degradation of ET-1 was observed only in the presence of the stimulated cells, leading to the generation of seven radiolabelled peaks. Addition of phosphoramidon had no effect on the appearance of these metabolites, while soybean trypsin inhibitor abolished almost completely the degradation of the peptide, suggesting a role of cathepsin G in ET-1 hydrolysis. Among the purified leukocyte enzymes tested, cathepsin G hydrolyzed I-125-labelled ET-1 at the higher rate and gave rise to two radiolabelled peaks already observed in the presence of activated PMN. Incubation of unlabelled ET-I with purified cathepsin G allowed to identify a major cleavage site corresponding to the His16-Leu17 bond, leading to the formation of inactive [1-16] fragments and the C-terminal pentapeptide. This mechanism of ET-1 inactivation could play a role in acute inflammatory reaction where PMN adhere to the vascular endothelial cells.
引用
收藏
页码:27 / 37
页数:11
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