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Extracellular Secretion of Suppressor of Cytokine Signaling (SOCS) Proteins by Alveolar Macrophages (AMs)
Author(s) -
Bourdonnay Emilie,
Penke Loka Raghu Kumar,
PetersGolden Marc
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.603.2
Subject(s) - secretion , microbiology and biotechnology , socs3 , extracellular , microvesicles , intracellular , signal transduction , in vivo , exosome , cytokine , suppressor of cytokine signaling 1 , biology , chemistry , stat3 , biochemistry , immunology , suppressor , microrna , gene
Many proteins once thought to be exclusively intracellular have been shown to be secreted into the extracellular space via unconventional pathways. SOCS proteins serve as critical brakes on immune activation by targeting STAT proteins, and have never been identified in the extracellular space. Here we investigated i) if SOCS proteins are secreted by AMs in vitro and in vivo; ii) if secreted SOCS proteins are biologically active; and iii) if their secretion proceeds by conventional or unconventional pathways. SOCS1 and 3 proteins were secreted constitutively by primary rat AMs and this was not explained by toxicity. In vivo, SOCS3 could be identified in BAL fluid of naïve mice. SOCS‐enriched conditioned medium from AMs inhibited IL‐6‐induced STAT3 and IFNγ‐induced STAT1 protein phosphorylation/activation in rat lung epithelial cells. Monensin, an inhibitor of conventional secretion, decreased secretion of TNF‐α but not that of SOCS proteins, suggesting unconventional secretion mechanisms are involved. Differential centrifugation revealed that SOCS3 protein was found in microparticles rather than exosomes. These studies show that SOCS 1 and 3 are secreted from AMs in vitro and in vivo, via the release of microparticles. We speculate that this represents a novel means of intercellular communication by which AMs can modulate lung immunity, for example by inhibiting JAK/STAT pathway in epithelial cells. This work was supported by U.S. National Institutes of Health grant HL058897 (M.P.‐G.) and an American Lung Association Senior Research Training Fellowship (E.B.).