Journal article
Identification of a Novel Splice Variant Isoform of TREM-1 in Human Neutrophil Granules
The Journal of immunology (1950), Vol.195(12), pp.5725-5731
12/15/2015
DOI: 10.4049/jimmunol.1402713
PMCID: PMC4670805
PMID: 26561551
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.
Details
- Title: Subtitle
- Identification of a Novel Splice Variant Isoform of TREM-1 in Human Neutrophil Granules
- Creators
- Sankar Baruah - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242Kathy Keck - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242Michelle Vrenios - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242Marshall R Pope - Carver College of Medicine Proteomics Facility, University of Iowa, Iowa City, IA 52242; andMerideth Pearl - Veenstra & Kimm, Inc., Coralville, IA 52241Kevin Doerschug - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242Julia Klesney-Tait - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242; julia-klesney-tait@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.195(12), pp.5725-5731
- DOI
- 10.4049/jimmunol.1402713
- PMID
- 26561551
- PMCID
- PMC4670805
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- P30 ES005605 / NIEHS NIH HHS R01 HL121105 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/15/2015
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Medicine Administration; Internal Medicine
- Record Identifier
- 9984094332502771
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