title: TREM-like transcript 2 is stored in human neutrophil primary granules and is up-regulated in response to inflammatory mediators.
abstract: The triggering receptor expressed on myeloid cell locus encodes a family of receptors that is emerging as an important class of molecules involved in modulating the innate immune response and inflammation. Of the 4 conserved members, including triggering receptor expressed on myeloid cells 1 and 2 and triggering receptor expressed on myeloid cell-like transcripts 1 and 2, relatively little is known about triggering receptor expressed on myeloid cell-like transcript 2 expression and function, particularly in humans. In this study, experiments were performed to determine if triggering receptor expressed on myeloid cell-like transcript 2 expression is conserved between mouse and human, demonstrating that human triggering receptor expressed on myeloid cell-like transcript 2 is expressed on cells of the lymphoid, as well as myeloid/granuloid lineages, similar to murine triggering receptor expressed on myeloid cell-like transcript 2. Consistent with studies in the mouse, triggering receptor expressed on myeloid cell-like transcript 2 expression is up-regulated in response to inflammatory mediators on human neutrophils. Importantly, it was shown that triggering receptor expressed on myeloid cell-like transcript 2, in resting human neutrophils, is predominantly localized to intracellular vesicles, including secretory vesicles and primary granules; with the majority of triggering receptor expressed on myeloid cell-like transcript 2 stored in primary granules. In contrast to other primary granule proteins, triggering receptor expressed on myeloid cell-like transcript 2 is not expelled on neutrophil extracellular traps but is retained in the plasma membrane following primary granule exocytosis. In summary, these findings establish that triggering receptor expressed on myeloid cell-like transcript 2 expression is conserved between species and is likely to be important in regulating neutrophil antimicrobial function following primary granule exocytosis.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California, USA;
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Thomas
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Alabama, USA; and.
authors.forename: R Glenn
authors.initials: RG
authors.lastname: King
authors.affiliation: Department of Biology, University of Montevallo, Alabama, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Sestero
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Alabama, USA; and lbjust@uab.edu.
authors.forename: Louis B
authors.initials: LB
authors.lastname: Justement
mesh_terms: D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D022142:Secretory Vesicles / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D011971:Receptors, Immunologic; C473367:TREML2 protein, human
keywords: TLT2; exocytosis; leukocyte