Release of full-length 55-kDa TNF receptor 1 in exosome-like vesicles: A mechanism for generation of soluble cytokine receptors

Feras I. Hawari, Farshid N. Rouhani, Xinle Cui, Zu Xi Yu, Caitriona Buckley, Maryann Kaler, Stewart J. Levine

    Research output: Contribution to journalArticle

    138 Scopus citations

    Abstract

    Soluble tumor necrosis factor receptors (TNFRs) are important modulators of TNF bioactivity. Proteolytic cleavage of the 28-kDa ectodomain of TNFR1 has been recognized as the mechanism by which soluble TNFR is shed. We now describe the release of exosome-like vesicles as a mechanism for the generation of soluble, full-length 55-kDa TNFR1. We found unexpectedly that the predominant form of soluble TNFR1 in human serum and lung epithelial lining fluid is a full-length 55-kDa protein. Furthermore, supernatants from human vascular endothelial cells contain only full-length 55-kDa TNFR1 that can be sedimented by high-speed centrifugation, floated on sucrose gradients at a density of 1.1 g/ml, and associated with vesicles that range in diameter from 20 nm to 50 nm. We conclude that the release of TNFR1 exosome-like vesicles represents a previously unrecognized mechanism by which constitutive production of soluble cytokine receptors may be regulated, independent of ectodomain cleavage by receptor sheddases.

    Original languageEnglish (US)
    Pages (from-to)1297-1302
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume101
    Issue number5
    DOIs
    StatePublished - Feb 3 2004

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