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Identification of a Novel Splice Variant Isoform of TREM-1 in Human Neutrophil Granules.

ABSTRACT: Triggering receptor expressed on myeloid cells-1 (TREM-1) is critical for inflammatory signal amplification. Humans have two forms of TREM-1: a membrane receptor, associated with the adaptor DAP12, and a soluble receptor detected at times of infection. The membrane receptor isoform acts synergistically with the TLR pathway to promote cytokine secretion and neutrophil migration, whereas the soluble receptor functions as a counterregulatory molecule. In multiple models of sepsis, exogenous administration of soluble forms of TREM-1 attenuates inflammation and markedly improves survival. Despite intense interest in soluble TREM-1, both as a clinical predictor of survival and as a therapeutic tool, the origin of native soluble TREM-1 remains controversial. Using human neutrophils, we identified a 15-kDa TREM-1 isoform in primary (azurophilic) and secondary (specific) granules. Mass spectrometric analysis, ELISA, and immunoblot confirm that the 15-kDa protein is a novel splice variant form of TREM-1 (TREM-1sv). Neutrophil stimulation with Pseudomonas aeruginosa, LPS, or PAM(3)Cys4 resulted in degranulation and release of TREM-1sv. The addition of exogenous TREM-1sv inhibited TREM-1 receptor-mediated proinflammatory cytokine production. Thus, these data reveal that TREM-1 isoforms simultaneously activate and inhibit inflammation via the canonical membrane TREM-1 molecule and this newly discovered granular isoform, TREM-1sv.

SUBMITTER: Baruah S

PROVIDER: S-EPMC4670805 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Identification of a Novel Splice Variant Isoform of TREM-1 in Human Neutrophil Granules.

Baruah Sankar S Keck Kathy K Vrenios Michelle M Pope Marshall R MR Pearl Merideth M Doerschug Kevin K Klesney-Tait Julia J

Journal of immunology (Baltimore, Md. : 1950) 20151111 12

Triggering receptor expressed on myeloid cells-1 (TREM-1) is critical for inflammatory signal amplification. Humans have two forms of TREM-1: a membrane receptor, associated with the adaptor DAP12, and a soluble receptor detected at times of infection. The membrane receptor isoform acts synergistically with the TLR pathway to promote cytokine secretion and neutrophil migration, whereas the soluble receptor functions as a counterregulatory molecule. In multiple models of sepsis, exogenous adminis ...[more]

PMID: 26561551

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Dataset Information

Identification of a Novel Splice Variant Isoform of TREM-1 in Human Neutrophil Granules.

Publications

Identification of a Novel Splice Variant Isoform of TREM-1 in Human Neutrophil Granules.

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