TY - JOUR
T1 - TREM-like transcript 2 is stored in human neutrophil primary granules and is up-regulated in response to inflammatory mediators
AU - Thomas, Kimberly A.
AU - King, R. Glenn
AU - Sestero, Christine M.
AU - Justement, Louis B.
N1 - Funding Information:
This study was supported, in part, by the U.S. National Institutes of Health (NIH) Grant AI107232-01 (to L.B.J.). The authors thank the laboratories of Chad Steele, Amit Gaggar, Phillip Smith, and Zdenek Hel at University of Alabama at Birmingham (UAB) for the use of equipment and sharing of reagents. The authors also thank Christine Sestero and Preeyam Patel for sample isolation and Mary Ann Accavatti-Loper of the UAB Hybridoma Core for mAb generation and Shawn Williams of the UAB High Resolution Imaging Core (both supported by NIH Grant P30 AR048311).
Publisher Copyright:
© Society for Leukocyte Biology.
PY - 2016/7
Y1 - 2016/7
N2 - 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 celllike 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.
AB - 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 celllike 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.
KW - Exocytosis
KW - Leukocyte
KW - TLT2
UR - http://www.scopus.com/inward/record.url?scp=84976537543&partnerID=8YFLogxK
U2 - 10.1189/jlb.3AB1115-507R
DO - 10.1189/jlb.3AB1115-507R
M3 - Article
C2 - 26753760
AN - SCOPUS:84976537543
VL - 100
SP - 177
EP - 184
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 1
ER -