Rapid secretion of interleukin-1beta by microvesicle shedding.
The proinflammatory cytokine interleukin-1beta (IL-1beta) 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-1beta, which only later appeared in the vesicle-free supernatant. We conclude that microvesicle shedding is a major secretory pathway for rapid IL-1beta release from activated monocytes and may represent a more general mechanism for secretion of similar leaderless secretory proteins.
MacKenzie
A
A
Institute of Molecular Physiology, University of Sheffield, Sheffield S10 2TN, United Kingdom.
Wilson
H L
HL
Kiss-Toth
E
E
Dower
S K
SK
North
R A
RA
Surprenant
A
A
D002460:Cell Line; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology* / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000276:immunology* / Q000648:ultrastructure; D022142:Secretory Vesicles / Q000276:immunology / Q000648:ultrastructure
D007375:Interleukin-1