Rapid secretion of interleukin-1 beta by microvesicle shedding

The proinflammatory cytokine interleukin-1 beta (IL-1 beta) is a secreted p rotein that lacks a signal peptide and does not follow currently known path ways of secretion. Its efficient release from activated immune cells requir es a secondary stimulus such as extracellular ATP acting on P2X(7) receptor s. 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 tha t microvesicle shedding is a major secretory pathway for rapid IL-1 beta re lease from activated monocytes and may represent a more general mechanism f or secretion of similar leaderless secretory proteins.