PMID- 33565143
OWN - NLM
STAT- MEDLINE
DCOM- 20210928
LR  - 20220531
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Linking)
VI  - 99
IP  - 6
DP  - 2021 Jul
TI  - Adhesion to E-selectin primes macrophages for activation through AKT and mTOR.
PG  - 622-639
LID - 10.1111/imcb.12447 [doi]
AB  - The endothelial adhesion protein E-selectin/CD62E is not required for leukocyte 
      homing, unlike closely related family member P-selectin/CD62P. As transmigration 
      through the endothelium is one of the first steps in generating a local immune 
      response, we hypothesized that E-selectin may play additional roles in the early 
      stages of immune activation. We found contact with E-selectin, but not P-selectin 
      or vascular cell adhesion molecule 1 (CD106), induced phosphorylation of protein 
      kinase B (AKT) and nuclear factor-kappaB in mouse bone marrow-derived macrophages 
      (BMDMs) in vitro. This occurred within 15 min of E-selectin contact and was 
      dependent on phosphatidylinositol-3 kinase activity. Binding to E-selectin 
      activated downstream proteins including mammalian target of rapamycin, p70 
      ribosomal protein S6 kinase and eukaryotic translation initiation factor 
      4E-binding protein 1. Functionally, adhesion to E-selectin induced upregulation 
      of CD86 expression and CCL2 secretion. We next asked whether contact with 
      E-selectin impacts further BMDM stimulation. We found enhanced secretion of both 
      interleukin (IL)-10 and CCL2, but not tumor necrosis factor or IL-6 in response 
      to lipopolysaccharide (LPS) stimulation after adhesion to E-selectin. 
      Importantly, adhesion to E-selectin did not polarize BMDMs to one type of 
      response but enhanced both arginase activity and nitric oxide production 
      following IL-4 or LPS stimulation, respectively. In cultured human monocytes, 
      adhesion to E-selectin similarly induced phosphorylation of AKT. Finally, when 
      E-selectin was blocked in vivo in mice, thioglycollate-elicited macrophages 
      showed reduced CD86 expression, validating our in vitro studies. Our results 
      imply functions for E-selectin beyond homing and suggest that E-selectin plays an 
      early role in priming and amplifying innate immune responses.
CI  - (c) 2021 Australian and New Zealand Society for Immunology Inc.
FAU - Davies, Julie M
AU  - Davies JM
AUID- ORCID: 0000-0003-4035-6047
AD  - Mater Research Institute, Translational Research Institute, The University of 
      Queensland, Woolloongabba, QLD, Australia.
FAU - Radford, Kristen J
AU  - Radford KJ
AUID- ORCID: 0000-0001-6512-6323
AD  - Mater Research Institute, Translational Research Institute, The University of 
      Queensland, Woolloongabba, QLD, Australia.
FAU - Begun, Jakob
AU  - Begun J
AUID- ORCID: 0000-0001-5256-7672
AD  - Mater Research Institute, Translational Research Institute, The University of 
      Queensland, Woolloongabba, QLD, Australia.
FAU - Levesque, Jean-Pierre
AU  - Levesque JP
AUID- ORCID: 0000-0002-7299-6025
AD  - Mater Research Institute, Translational Research Institute, The University of 
      Queensland, Woolloongabba, QLD, Australia.
FAU - Winkler, Ingrid G
AU  - Winkler IG
AUID- ORCID: 0000-0001-6026-3572
AD  - Mater Research Institute, Translational Research Institute, The University of 
      Queensland, Woolloongabba, QLD, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210309
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (E-Selectin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Adhesion
MH  - Cells, Cultured
MH  - *E-Selectin
MH  - Endothelium, Vascular
MH  - Macrophages
MH  - Mice
MH  - *Proto-Oncogene Proteins c-akt
MH  - TOR Serine-Threonine Kinases
OTO - NOTNLM
OT  - AKT
OT  - CCL2
OT  - E-selectin
OT  - adhesion molecules
OT  - mTOR
OT  - macrophage activation
EDAT- 2021/02/11 06:00
MHDA- 2021/09/29 06:00
CRDT- 2021/02/10 06:01
PHST- 2021/02/08 00:00 [revised]
PHST- 2020/11/05 00:00 [received]
PHST- 2021/02/08 00:00 [accepted]
PHST- 2021/02/11 06:00 [pubmed]
PHST- 2021/09/29 06:00 [medline]
PHST- 2021/02/10 06:01 [entrez]
AID - 10.1111/imcb.12447 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2021 Jul;99(6):622-639. doi: 10.1111/imcb.12447. Epub 2021 Mar 
      9.