Rapid secretion of interleukin-1β by microvesicle shedding

被引:730
作者
MacKenzie, A
Wilson, HL
Kiss-Toth, E
Dower, SK
North, RA
Surprenant, A [1 ]
机构
[1] Univ Sheffield, Inst Mol Physiol, Sheffield S10 2TN, S Yorkshire, England
[2] Univ Sheffield, Sect Funct Genom, Sheffield S10 2TN, S Yorkshire, England
基金
英国惠康基金;
关键词
D O I
10.1016/S1074-7613(01)00229-1
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The proinflammatory cytokine interleukin-1 beta (IL-1 beta) is a secreted protein that lacks a signal peptide and does not follow currently known pathways of secretion. Its efficient release from activated immune cells requires a secondary stimulus such as extracellular ATP acting on P2X(7) receptors. We show that human THP-1 monocytes shed microvesicles from their plasma membrane within 2-5 s of activation of P2X(7) receptors. Two minutes after such stimulation, the released microvesicles contained bioactive IL-1 beta, which only later appeared in the vesicle-free supernatant. We conclude that microvesicle shedding is a major secretory pathway for rapid IL-1 beta release from activated monocytes and may represent a more general mechanism for secretion of similar leaderless secretory proteins.
引用
收藏
页码:825 / 835
页数:11
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