Adhesion to E-selectin primes macrophages for activation through AKT and mTOR.
AKT
CCL2
E-selectin
adhesion molecules
mTOR
macrophage activation
Journal
Immunology and cell biology
ISSN: 1440-1711
Titre abrégé: Immunol Cell Biol
Pays: United States
ID NLM: 8706300
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
08
02
2021
received:
05
11
2020
accepted:
08
02
2021
pubmed:
11
2
2021
medline:
29
9
2021
entrez:
10
2
2021
Statut:
ppublish
Résumé
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-κB 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.
Substances chimiques
E-Selectin
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
622-639Informations de copyright
© 2021 Australian and New Zealand Society for Immunology Inc.
Références
McEver RP. Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res 2015; 107: 331-339.
Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 2014; 6: 13.
Hume DA. The many alternative faces of macrophage activation. Front Immunol 2015; 6: 370.
Rath M, Muller I, Kropf P, Closs EI, Munder M. Metabolism via Arginase or nitric oxide synthase: two competing arginine pathways in macrophages. Front Immunol 2014; 5: 532.
Robinson SD, Frenette PS, Rayburn H, et al. Multiple, targeted deficiencies in selectins reveal a predominant role for P-selectin in leukocyte recruitment. Proc Natl Acad Sci USA 1999; 96: 11452-11457.
Frenette PS, Mayadas TN, Rayburn H, Hynes RO, Wagner DD. Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins. Cell 1996; 84: 563-574.
Bullard DC, Kunkel EJ, Kubo H, et al. Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice. J Exp Med 1996; 183: 2329-2336.
Koni PA, Joshi SK, Temann UA, Olson D, Burkly L, Flavell RA. Conditional vascular cell adhesion molecule 1 deletion in mice: impaired lymphocyte migration to bone marrow. J Exp Med 2001; 193: 741-754.
Leuker CE, Labow M, Muller W, Wagner N. Neonatally induced inactivation of the vascular cell adhesion molecule 1 gene impairs B cell localization and T cell-dependent humoral immune response. J Exp Med 2001; 193: 755-768.
Mayadas TN, Johnson RC, Rayburn H, Hynes RO, Wagner DD. Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell 1993; 74: 541-554.
Labow MA, Norton CR, Rumberger JM, et al. Characterization of E-selectin-deficient mice: demonstration of overlapping function of the endothelial selectins. Immunity 1994; 1: 709-720.
Winkler IG, Barbier V, Nowlan B, et al. Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance. Nat Med 2012; 18: 1651-1657.
Barbier V, Erbani J, Fiveash C, et al. Endothelial E-selectin inhibition improves acute myeloid leukaemia therapy by disrupting vascular niche-mediated chemoresistance. Nat Commun 2020; 11: 2042.
Simon SI, Hu Y, Vestweber D, Smith CW. Neutrophil tethering on E-selectin activates β2 integrin binding to ICAM-1 through a mitogen-activated protein kinase signal transduction pathway. J Immunol 2000; 164: 4348-4358.
Zarbock A, Lowell CA, Ley K. Spleen tyrosine kinase Syk is necessary for E-selectin-induced αLβ2 integrin-mediated rolling on intercellular adhesion molecule-1. Immunity 2007; 26: 773-783.
Morikis VA, Chase S, Wun T, Chaikof EL, Magnani JL, Simon SI. Selectin catch-bonds mechanotransduce integrin activation and neutrophil arrest on inflamed endothelium under shear flow. Blood 2017; 130: 2101-2110.
Gong Y, Zhang Y, Feng S, Liu X, Lü S, Long M. Dynamic contributions of P- and E-selectins to β2-integrin-induced neutrophil transmigration. FASEB J 2017; 31: 212-223.
Chase SD, Magnani JL, Simon SI. E-selectin ligands as mechanosensitive receptors on neutrophils in health and disease. Ann Biomed Eng 2012; 40: 849-59.
Abbassi O, Kishimoto TK, McIntire LV, Anderson DC, Smith CW. E-selectin supports neutrophil rolling in vitro under conditions of flow. J Clin Invest 1993; 92: 2719-2730.
Luo J, Xu T, Wang X, et al. PI3K is involved in L-selectin- and PSGL-1-mediated neutrophil rolling on E-selectin via F-actin redistribution and assembly. J Cell Biochem 2010; 110: 910-919.
Snapp KR, Heitzig CE, Kansas GS. Attachment of the PSGL-1 cytoplasmic domain to the actin cytoskeleton is essential for leukocyte rolling on P-selectin. Blood 2002; 99: 4494-4502.
Jean S, Kiger AA. Classes of phosphoinositide 3-kinases at a glance. J Cell Sci 2014; 127: 923-928.
Weichhart T, Hengstschlager M, Linke M. Regulation of innate immune cell function by mTOR. Nat Rev Immunol 2015; 15: 599-614.
Stacey KJ, Young GR, Clark F, et al. The molecular basis for the lack of immunostimulatory activity of vertebrate DNA. J Immunol 2003; 170: 3614-3620.
Dai J, Jiang C, Chen H, Chai Y. Rapamycin Attenuates High Glucose-Induced Inflammation Through Modulation of mTOR/NF-κB Pathways in Macrophages. Front Pharmacol 2019; 10: 1292.
Sizemore N, Lerner N, Dombrowski N, Sakurai H, Stark GR. Distinct roles of the IκB kinase α and β subunits in liberating nuclear factor κB (NF-κB) from IκB and in phosphorylating the p65 subunit of NF-κB. J Biol Chem 2002; 277: 3863-3869.
Madrid LV, Mayo MW, Reuther JY, Baldwin AS Jr. Akt stimulates the transactivation potential of the RelA/p65 subunit of NF-κB through utilization of the IκB kinase and activation of the mitogen-activated protein kinase p38. J Biol Chem 2001; 276: 18934-18940.
Dan HC, Cooper MJ, Cogswell PC, Duncan JA, Ting JP, Baldwin AS. Akt-dependent regulation of NF-κB is controlled by mTOR and Raptor in association with IKK. Genes Dev 2008; 22: 1490-1500.
Ai D, Jiang H, Westerterp M, et al. Disruption of mammalian target of rapamycin complex 1 in macrophages decreases chemokine gene expression and atherosclerosis. Circ Res 2014; 114: 1576-1584.
Jorgensen PF, Wang JE, Almlof M, et al. Sirolimus interferes with the innate response to bacterial products in human whole blood by attenuation of IL-10 production. Scand J Immunol 2001; 53: 184-191.
Ohtani M, Nagai S, Kondo S, et al. Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cells. Blood 2008; 112: 635-643.
Stanley ER, Guilbert LJ, Tushinski RJ, Bartelmez SH. CSF-1-a mononuclear phagocyte lineage-specific hemopoietic growth factor. J Cell Biochem 1983; 21: 151-159.
Lombardo E, Alvarez-Barrientos A, Maroto B, Bosca L, Knaus UG. TLR4-mediated survival of macrophages is MyD88 dependent and requires TNF-α autocrine signalling. J Immunol 2007; 178: 3731-3739.
Natoni A, Smith TAG, Keane N, et al. E-selectin ligands recognised by HECA452 induce drug resistance in myeloma, which is overcome by the E-selectin antagonist, GMI-1271. Leukemia 2017; 31: 2642-2651.
Sonika GP, Rahul K, Herkt SC, et al. The vascular bone marrow niche influences outcome in chronic myeloid leukemia via the E-selectin - SCL/TAL1 - CD44 axis. Haematologica 2020; 105: 136-147.
Ghosn EE, Cassado AA, Govoni GR, et al. Two physically, functionally, and developmentally distinct peritoneal macrophage subsets. Proc Natl Acad Sci USA 2010; 107: 2568-2573.
Cain DW, O'Koren EG, Kan MJ, et al. Identification of a tissue-specific, C/EBPβ-dependent pathway of differentiation for murine peritoneal macrophages. J Immunol 2013; 191: 4665-4675.
Okabe Y, Medzhitov R. Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell 2014; 157: 832-844.
Porquet N, Poirier A, Houle F, et al. Survival advantages conferred to colon cancer cells by E-selectin-induced activation of the PI3K-NFκB survival axis downstream of Death receptor-3. BMC Cancer 2011; 11: 285.
Williams MR, Sakurai Y, Zughaier SM, Eskin SG, McIntire LV. Transmigration across activated endothelium induces transcriptional changes, inhibits apoptosis, and decreases antimicrobial protein expression in human monocytes. J Leukoc Biol 2009; 86: 1331-1343.
Haraldsen G, Kvale D, Lien B, Farstad IN, Brandtzaeg P. Cytokine-regulated expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in human microvascular endothelial cells. J Immunol 1996; 156: 2558-2565.
Jiang Y, Zhu JF, Luscinskas FW, Graves DT. MCP-1-stimulated monocyte attachment to laminin is mediated by beta 2-integrins. Am J Physiol 1994; 267: C1112-C1118.
Gerszten RE, Garcia-Zepeda EA, Lim YC, et al. MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature 1999; 398: 718-723.
Melzi R, Maffi P, Nano R, et al. Rapamycin does not adversely affect intrahepatic islet engraftment in mice and improves early islet engraftment in humans. Islets 2009; 1: 42-49.
Gunzl P, Bauer K, Hainzl E, et al. Anti-inflammatory properties of the PI3K pathway are mediated by IL-10/DUSP regulation. J Leukoc Biol 2010; 88: 1259-1269.
Beg AA, Baltimore D. An essential role for NF-κB in preventing TNF-α-induced cell death. Science 1996; 274: 782-784.
Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS Jr. NF-κB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 1998; 281: 1680-1683.
Karin M, Lin A. NF-κB at the crossroads of life and death. Nat Immunol 2002; 3: 221-227.
Marte BM, Downward J. PKB/Akt: connecting phosphoinositide 3-kinase to cell survival and beyond. Trends Biochem Sci 1997; 22: 355-358.
Kennedy SG, Wagner AJ, Conzen SD, et al. The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev 1997; 11: 701-713.
Romashkova JA, Makarov SS. NF-κB is a target of AKT in anti-apoptotic PDGF signalling. Nature 1999; 401: 86-90.
Watson RW, Rotstein OD, Nathens AB, Parodo J, Marshall JC. Neutrophil apoptosis is modulated by endothelial transmigration and adhesion molecule engagement. J Immunol 1997; 158: 945-953.
Maj T, Slawek A, Chelmonska-Soyta A. CD80 and CD86 costimulatory molecules differentially regulate OT-II CD4+ T lymphocyte proliferation and cytokine response in cocultures with antigen-presenting cells derived from pregnant and pseudopregnant mice. Mediators Inflamm 2014; 2014: 769239.
Devata S, Angelini DE, Blackburn S, et al. Use of GMI-1271, an E-selectin antagonist, in healthy subjects and in 2 patients with calf vein thrombosis. Res Pract Thromb Haemost 2020; 4: 193-204.
Esposito M, Mondal N, Greco TM, et al. Bone vascular niche E-selectin induces mesenchymal-epithelial transition and Wnt activation in cancer cells to promote bone metastasis. Nat Cell Biol 2019; 21: 627-639.
Manzanero S. Generation of mouse bone marrow-derived macrophages. Methods Mol Biol 2012; 844: 177-181.
Winkler IG, Snapp KR, Simmons PJ, Levesque JP. Adhesion to E-selectin promotes growth inhibition and apoptosis of human and murine hematopoietic progenitor cells independent of PSGL-1. Blood 2004; 103: 1685-1692.
Corraliza IM, Campo ML, Soler G, Modolell M. Determination of arginase activity in macrophages: a micromethod. J Immunol Methods 1994; 174: 231-235.
Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm 2016; 7: 27-31.