title: Toll-Like Receptor induced CD11b and L-selectin response in patients with coronary artery disease.
abstract: Toll-Like Receptor (TLR) -2 and -4 expression and TLR-induced cytokine response of inflammatory cells are related to atherogenesis and atherosclerotic plaque progression. We examined whether immediate TLR induced changes in CD11b and L-selectin (CD62L) expression are able to discriminate the presence and severity of atherosclerotic disease by exploring single dose whole blood TLR stimulation and detailed dose-response curves. Blood samples were obtained from 125 coronary artery disease (CAD) patients and 28 controls. CD11b and L-selectin expression on CD14+ monocytes was measured after whole blood stimulation with multiple concentrations of the TLR4 ligand LPS (0.01-10 ng/ml) and the TLR2 ligand P3C (0.5-500 ng/ml). Subsequently, dose-response curves were created and the following parameters were calculated: hillslope, EC50, area under the curve (AUC) and delta. These parameters provide information about the maximum response following activation, as well as the minimum trigger required to induce activation and the intensity of the response. CAD patients showed a significantly higher L-selectin, but not CD11b response to TLR ligation than controls after single dose stimulations as well as significant differences in the hillslope and EC50 of the dose-response curves. Within the CAD patient group, dose-response curves of L-selectin showed significant differences in the presence of hypertension, dyslipidemia, coronary occlusion and degree of stenosis, whereas CD11b expression had the strongest discriminating power after single dose stimulation. In conclusion, single dose stimulations and dose-response curves of CD11b and L-selectin expression after TLR stimulation provide diverse but limited information about atherosclerotic disease severity in stable angina patients. However, both single dose stimulation and dose-response curves of LPS-induced L-selectin expression can discriminate between controls and CAD patients.
authors.affiliation: Laboratory of Experimental Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Ellen H A M
authors.initials: EH
authors.lastname: Elsenberg
authors.forename: Marieke A
authors.initials: MA
authors.lastname: Hillaert
authors.forename: Hester M
authors.initials: HM
authors.lastname: den Ruijter
authors.forename: Jan-Willem E M
authors.initials: JW
authors.lastname: Sels
authors.forename: Vincent P W
authors.initials: VP
authors.lastname: Scholtes
authors.forename: Hendrik M
authors.initials: HM
authors.lastname: Nathoe
authors.forename: Johan
authors.initials: J
authors.lastname: Kuiper
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000276:immunology; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019041:L-Selectin / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000502:physiology*
chemical_list: D039481:CD11b Antigen; C509295:ITGAM protein, human; D008070:Lipopolysaccharides; D008074:Lipoproteins; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine; D019041:L-Selectin