Divergent effects of α1-antitrypsin on neutrophil activation, in vitro

被引:35
作者
Janciauskiene, S [1 ]
Zelvyte, I
Jansson, L
Stevens, T
机构
[1] Malmo Univ Hosp, Dept Med, S-20502 Malmo, Sweden
[2] AstraZeneca R&D, Lund, Sweden
关键词
antitrypsin; C-36; peptide; inflammation; proteases; neutrophils; COPD;
D O I
10.1016/j.bbrc.2004.01.055
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
alphal-Antitrypsin (AAT) is a major circulating serine proteinase inhibitor in humans. The anti-proteinase activity of AAT is inhibited by chemical modification. These include inter- or intramolecular polymerisation, oxidation, complex formation with target proteinases (e.g., neutrophil elastase), and/or cleavage by multi-specific proteinases. In vivo, several modified forms of AAT have been identified which stimulate biological activity in vitro unrelated to inhibition of serine proteinases. In this study we have examined the effects of native and polymerised AAT and C-36 peptide, a proteolytic cleavage product of AAT, on human neutrophil activation, in vitro. We show that the C-36 peptide displays striking concentration-dependent pro-inflammatory effects on human neutrophils, including induction of neutrophil chemotaxis, adhesion, degranulation, and superoxide generation. In contrast to C-36 peptide, native and polymerised AAT at similar and higher concentrations showed no effects on neutrophil activation. These results suggest that cleavage of AAT may not only abolish its proteinase inhibitor activity, but can also generate a powerful pro-inflammatory activator for human neutrophils. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:288 / 296
页数:9
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