{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:47:26Z","timestamp":1789206446980,"version":"build-2803163510"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chronic recruitment of monocytes and their subsequent migration through the activated endothelium contribute to atherosclerotic plaque development. Integrin-mediated leukocyte adhesion is central to this process. Conjugated linoleic acid (CLA) has the unique property of inducing regression of pre-established murine atherosclerosis via modulation of monocyte\/macrophage function. Understanding the mechanisms through which CLA mediates its atheroprotective effect may help to identify novel pathways that limit or reverse atherosclerosis. In this study, we identified a novel mechanism through which CLA alters monocyte function. We show that CLA inhibits human peripheral blood monocyte cell adhesion to activated endothelial cells via loss of CD18 expression, the \u03b22 chain of LFA-1 and Mac-1 integrins. In addition, using a static-adhesion assay, we provide evidence that CLA prevents monocytes from binding to ICAM-1 and subsequently reduces the capacity of these cells to polarize. CXCL12\u2013CXCR4 interactions induce a conformational change in \u03b22 integrins, facilitating leukocyte adhesion. In this study, we demonstrate that CLA inhibits CXCR4 expression, resulting in a failure of monocytes to directionally migrate toward CXCL12. Finally, using intravital microscopy, we show that, during CLA-induced regression of pre-established atherosclerosis in ApoE\u2212\/\u2212 mice, there is reduced leukocyte adhesion and decreased CD18 expression on Gr1+\/CD115+ proinflammatory monocytes. In summary, the data presented describe a novel functional role for CLA in the regulation of monocyte adhesion, polarization, and migration.<\/jats:p>","DOI":"10.4049\/jimmunol.1300990","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T07:44:38Z","timestamp":1379576678000},"page":"4326-4336","source":"Crossref","is-referenced-by-count":21,"title":["Conjugated Linoleic Acid Targets \u03b22 Integrin Expression To Suppress Monocyte Adhesion"],"prefix":"10.1093","volume":"191","author":[{"given":"Monica","family":"de Gaetano","sequence":"first","affiliation":[{"name":"School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin , Dublin 4,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Dempsey","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin , Dublin 4,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Marcone","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin , Dublin 4,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G","family":"James","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin , Dublin 4,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orina","family":"Belton","sequence":"additional","affiliation":[{"name":"School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin , Dublin 4,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,10,15]]},"reference":[{"key":"2025032405460540400_r1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/labinvest.3700215","article-title":"The role of shear stress in the pathogenesis of atherosclerosis","volume":"85","author":"Cunningham","year":"2005","journal-title":"Lab. Invest."},{"key":"2025032405460540400_r2","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.mehy.2008.11.049","article-title":"New insights in atherosclerosis: endothelial shear stress as promoter rather than initiator","volume":"73","author":"Mehdizadeh","year":"2009","journal-title":"Med. Hypotheses"},{"key":"2025032405460540400_r3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nrm2596","article-title":"Mechanotransduction in vascular physiology and atherogenesis","volume":"10","author":"Hahn","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2025032405460540400_r4","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1161\/01.ATV.6.2.131","article-title":"Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque","volume":"6","author":"Jonasson","year":"1986","journal-title":"Arteriosclerosis"},{"key":"2025032405460540400_r5","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0021-9150(88)90074-3","article-title":"Localization of T lymphocytes and macrophages in fibrous and complicated human atherosclerotic plaques","volume":"72","author":"Hansson","year":"1988","journal-title":"Atherosclerosis"},{"key":"2025032405460540400_r6","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.cell.2011.04.005","article-title":"Macrophages in the pathogenesis of atherosclerosis","volume":"145","author":"Moore","year":"2011","journal-title":"Cell"},{"key":"2025032405460540400_r7","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nrcardio.2009.228","article-title":"Monocytes in atherosclerosis: subsets and functions","volume":"7","author":"Woollard","year":"2010","journal-title":"Nat Rev Cardiol"},{"key":"2025032405460540400_r8","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/19546","article-title":"MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions","volume":"398","author":"Gerszten","year":"1999","journal-title":"Nature"},{"key":"2025032405460540400_r9","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1084\/jem.193.10.1149","article-title":"Chemoattractants induce a rapid and transient upregulation of monocyte alpha4 integrin affinity for vascular cell adhesion molecule 1 which mediates arrest: an early step in the process of emigration","volume":"193","author":"Chan","year":"2001","journal-title":"J. Exp. Med."},{"key":"2025032405460540400_r10","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1146\/annurev.immunol.25.022106.141618","article-title":"Structural basis of integrin regulation and signaling","volume":"25","author":"Luo","year":"2007","journal-title":"Annu. Rev. Immunol."},{"key":"2025032405460540400_r11","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1083\/jcb.111.6.3129","article-title":"ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b\/CD18)","volume":"111","author":"Diamond","year":"1990","journal-title":"J. Cell Biol."},{"key":"2025032405460540400_r12","doi-asserted-by":"crossref","first-page":"7057","DOI":"10.4049\/jimmunol.1001638","article-title":"LFA-1 and Mac-1 define characteristically different intralumenal crawling and emigration patterns for monocytes and neutrophils in situ","volume":"185","author":"Sumagin","year":"2010","journal-title":"J. Immunol."},{"key":"2025032405460540400_r13","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s11745-999-0358-8","article-title":"Evidence that the trans-10,cis-12 isomer of conjugated linoleic acid induces body composition changes in mice","volume":"34","author":"Park","year":"1999","journal-title":"Lipids"},{"key":"2025032405460540400_r14","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.bbrc.2003.09.044","article-title":"Conjugated linoleic acid enhances plasma adiponectin level and alleviates hyperinsulinemia and hypertension in Zucker diabetic fatty (fa\/fa) rats","volume":"310","author":"Nagao","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2025032405460540400_r15","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/BF03179915","article-title":"Effects of conjugated linoleic acid on body fat accumulation and serum lipids in hamsters fed an atherogenic diet","volume":"59","author":"Navarro","year":"2003","journal-title":"J. Physiol. Biochem."},{"key":"2025032405460540400_r16","doi-asserted-by":"crossref","first-page":"472S","DOI":"10.1080\/07315724.2000.10718950","article-title":"Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits","volume":"19","author":"Kritchevsky","year":"2000","journal-title":"J. Am. Coll. Nutr."},{"key":"2025032405460540400_r17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0021-9150(94)90034-5","article-title":"Conjugated linoleic acid and atherosclerosis in rabbits","volume":"108","author":"Lee","year":"1994","journal-title":"Atherosclerosis"},{"issue":"6","key":"2025032405460540400_r18","doi-asserted-by":"crossref","first-page":"1199S","DOI":"10.1093\/ajcn\/79.6.1199S","article-title":"Immunomodulatory properties of conjugated linoleic acid","volume":"79","author":"O\u2019Shea","year":"2004","journal-title":"Am. J. Clin. Nutr."},{"key":"2025032405460540400_r19","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/biof.13","article-title":"Conjugated linoleic acid isomers: differences in metabolism and biological effects","volume":"35","author":"Churruca","year":"2009","journal-title":"Biofactors"},{"key":"2025032405460540400_r20","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.atherosclerosis.2005.08.024","article-title":"Profound resolution of early atherosclerosis with conjugated linoleic acid","volume":"187","author":"Toomey","year":"2006","journal-title":"Atherosclerosis"},{"key":"2025032405460540400_r21","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.atherosclerosis.2010.02.003","article-title":"Conjugated linoleic acid suppresses the migratory and inflammatory phenotype of the monocyte\/macrophage cell","volume":"211","author":"McClelland","year":"2010","journal-title":"Atherosclerosis"},{"key":"2025032405460540400_r22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S1388-1981(02)00126-9","article-title":"Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPAR gamma-dependent mechanism","volume":"1581","author":"Yu","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"2025032405460540400_r23","doi-asserted-by":"crossref","first-page":"11846","DOI":"10.1021\/jf2014233","article-title":"Conjugated linoleic acid regulates phosphorylation of PPAR\u03b3 by modulation of ERK 1\/2 and p38 signaling in human macrophages\/fatty acid-laden macrophages","volume":"59","author":"Stachowska","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"2025032405460540400_r24","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.domaniend.2011.05.005","article-title":"Trans-10, cis-12 conjugated linoleic acid and the PPAR-\u03b3 agonist rosiglitazone attenuate lipopolysaccharide-induced TNF-\u03b1 production by bovine immune cells","volume":"41","author":"Perdomo","year":"2011","journal-title":"Domest. Anim. Endocrinol."},{"key":"2025032405460540400_r25","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.2353\/ajpath.2009.080611","article-title":"Atherosclerosis in LDLR-knockout mice is inhibited, but not reversed, by the PPARgamma ligand pioglitazone","volume":"174","author":"Nakaya","year":"2009","journal-title":"Am. J. Pathol."},{"key":"2025032405460540400_r26","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nm1567","article-title":"MIF is a noncognate ligand of CXC chemokine receptors in ininflammatory and atherogenic cell recruitment","volume":"13","author":"Bernhagen","year":"2007","journal-title":"Nat. Med"},{"key":"2025032405460540400_r27","doi-asserted-by":"crossref","first-page":"6991","DOI":"10.4049\/jimmunol.176.11.6991","article-title":"Leukocyte recruitment to the inflamed glomerulus: a critical role for platelet-derived P-selectin in the absence of rolling","volume":"176","author":"Kuligowski","year":"2006","journal-title":"J Immunol"},{"key":"2025032405460540400_r28","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.atherosclerosis.2010.09.025","article-title":"SorLA modulates atheroprotective properties of CLA by regulating monocyte migration","volume":"213","author":"McCarthy","year":"2010","journal-title":"Atherosclerosis"},{"key":"2025032405460540400_r29","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1083\/jcb.116.1.219","article-title":"Divalent cation regulation of the function of the leukocyte integrin LFA-1","volume":"116","author":"Dransfield","year":"1992","journal-title":"J. Cell Biol."},{"key":"2025032405460540400_r30","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1002\/jcp.22478","article-title":"Analysis of dynamic tyrosine phosphoproteome in LFA-1 triggered migrating T-cells","volume":"226","author":"Verma","year":"2011","journal-title":"J. Cell. Physiol."},{"key":"2025032405460540400_r31","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1096\/fj.12-215442","article-title":"IL-10 mediates the immunoregulatory response in conjugated linoleic acid-induced regression of atherosclerosis","volume":"27","author":"McCarthy","year":"2013","journal-title":"FASEB J."},{"key":"2025032405460540400_r32","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1074-7613(03)00174-2","article-title":"Blood monocytes consist of two principal subsets with distinct migratory properties","volume":"19","author":"Geissmann","year":"2003","journal-title":"Immunity"},{"key":"2025032405460540400_r33","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/S0955-2863(02)00211-5","article-title":"Isomer-specific effects of conjugated linoleic acid (CLA) on adiposity and lipid metabolism","volume":"13","author":"Evans","year":"2002","journal-title":"J. Nutr. Biochem."},{"key":"2025032405460540400_r34","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1476-511X-8-15","article-title":"Effects of 9cis,11trans and 10trans,12cis CLA on osteoclast formation and activity from human CD14+ monocytes","volume":"8","author":"Platt","year":"2009","journal-title":"Lipids Health Dis."},{"key":"2025032405460540400_r35","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.nut.2007.10.018","article-title":"Conjugated linoleic acid increases intracellular ROS synthesis and oxygenation of arachidonic acid in macrophages","volume":"24","author":"Stachowska","year":"2008","journal-title":"Nutrition"},{"key":"2025032405460540400_r36","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/jn\/136.2.353","article-title":"Trans-10, cis-12- and cis-9, trans-11-conjugated linoleic acid isomers selectively modify HDL-apolipoprotein composition in apolipoprotein E knockout mice","volume":"136","author":"Arbon\u00e9s-Mainar","year":"2006","journal-title":"J. Nutr."},{"key":"2025032405460540400_r37","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3109\/09637486.2011.593505","article-title":"Conjugated linoleic acid isomers may diminish human macrophages adhesion to endothelial surface","volume":"63","author":"Stachowska","year":"2012","journal-title":"Int. J. Food Sci. Nutr."},{"key":"2025032405460540400_r38","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1073\/pnas.94.7.3162","article-title":"Folding of the beta-propeller domain of the integrin alphaL subunit is independent of the I domain and dependent on the beta2 subunit","volume":"94","author":"Huang","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032405460540400_r39","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1159\/000126054","article-title":"The synthetic PPARgamma agonist troglitazone inhibits eotaxin-enhanced eosinophil adhesion to ICAM-1-coated plates","volume":"146","author":"Hirasawa","year":"2008","journal-title":"Int. Arch. Allergy Immunol."},{"key":"2025032405460540400_r40","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1084\/jem.184.3.1101","article-title":"A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)","volume":"184","author":"Bleul","year":"1996","journal-title":"J. Exp. Med."},{"key":"2025032405460540400_r41","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1161\/01.RES.86.2.131","article-title":"The stromal cell-derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques","volume":"86","author":"Abi-Younes","year":"2000","journal-title":"Circ. Res."},{"key":"2025032405460540400_r42","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1002\/mc.20429","article-title":"Troglitazone inhibits cell migration, adhesion, and spreading by modulating cytoskeletal rearrangement in human breast cancer cells","volume":"47","author":"Wang","year":"2008","journal-title":"Mol. Carcinog."},{"key":"2025032405460540400_r43","doi-asserted-by":"crossref","first-page":"11846","DOI":"10.1021\/jf2014233","article-title":"Conjugated linoleic acid regulates phosphorylation of PPAR\u03b3 by modulation of ERK 1\/2 and p38 signaling in human macrophages\/fatty acid-laden macrophages","volume":"59","author":"Stachowska","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"2025032405460540400_r44","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1021\/jf0348626","article-title":"Contribution of conjugated linoleic acid to the suppression of inflammatory responses through the regulation of the NF-kappaB pathway","volume":"52","author":"Cheng","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"2025032405460540400_r45","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/icb.2008.19","article-title":"Blood monocytes: distinct subsets, how they relate to dendritic cells, and their possible roles in the regulation of T-cell responses","volume":"86","author":"Geissmann","year":"2008","journal-title":"Immunol. Cell Biol."},{"key":"2025032405460540400_r46","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1126\/science.1142883","article-title":"Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior","volume":"317","author":"Auffray","year":"2007","journal-title":"Science"},{"key":"2025032405460540400_r47","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1172\/JCI29950","article-title":"Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata","volume":"117","author":"Swirski","year":"2007","journal-title":"J. Clin. Invest."},{"key":"2025032405460540400_r48","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.atherosclerosis.2012.09.013","article-title":"Distribution of macrophage polarization markers in human atherosclerosis","volume":"225","author":"St\u00f6ger","year":"2012","journal-title":"Atherosclerosis"},{"key":"2025032405460540400_r49","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1161\/ATVBAHA.108.180497","article-title":"Macrophage diversity and polarization in atherosclerosis: a question of balance","volume":"29","author":"Mantovani","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/8\/4326\/62511047\/1300990.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/8\/4326\/62511047\/1300990.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T06:24:54Z","timestamp":1742883894000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/191\/8\/4326\/7966497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10]]},"references-count":49,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2013,10,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1300990","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,10]]},"published":{"date-parts":[[2013,10]]}}}