title: Toll-like receptor 2 and 4 response and expression on monocytes decrease rapidly in patients undergoing arterial surgery and are related to preoperative smoking.
abstract: Previously, we have shown that small arterial trauma is accompanied by a decreased capability of both toll-like receptors (TLRs) 2 and 4 to respond to stimulation with their respective ligands Pam3Cys and LPS. In this study, we assessed whether surgical arterial trauma induces a decrease in the TLR response and investigated the time course of the altered responsiveness. In addition, TLR responsiveness was related to baseline patient characteristics. Patients undergoing arterial surgery were included in the study. Patients undergoing pacemaker replacement served as control. Blood samples were drawn before, during, and immediately after vascular surgery and 24 h postoperatively. In all samples, we measured TLR-2 and TLR-4 expression using flow cytometry. Whole-blood samples were incubated with 5, 50, and 500 ng/mL Pam3Cys and with 1, 10, and 100 ng/mL LPS. Toll-like receptor response was assessed by measuring TNF-alpha in the supernatant with an enzyme-linked immune fluorescent assay. We observed a dose-dependent response in TNF-alpha production after stimulation with both LPS and Pam3Cys (P < 0.001). The TLR response decreased significantly after arterial trauma (P = 0.022). This effect on TLR response persisted in the 24-h postoperative period, whereas no such effect was observed in the control group. Toll-like receptor 2 expression decreased significantly immediately after surgery (P = 0.005) but increased 24 h after surgery (P < 0.001). Furthermore, an inverse relation between the TLR response and smoking was observed (P = 0.026). Toll-like receptor 2 and 4 response declines rapidly after arterial trauma in patients undergoing vascular surgery. These results point to a significant role for TLRs in the induction of postoperative immune tolerance. Furthermore, smoking is negatively related to baseline TLR response.
authors.affiliation: Experimental Cardiology Laboratory, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Dik
authors.initials: D
authors.lastname: Versteeg
authors.forename: Erik
authors.initials: E
authors.lastname: Dol
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.forename: Suzanne
authors.initials: S
authors.lastname: Flier
authors.forename: Wolfgang F
authors.initials: WF
authors.lastname: Buhre
authors.forename: Dominique
authors.initials: D
authors.lastname: de Kleijn
authors.forename: Eric P
authors.initials: EP
authors.lastname: van Dongen
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: de Vries
mesh_terms: D000368:Aged; D001158:Arteries / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008074:Lipoproteins / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects / Q000276:immunology / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D014656:Vascular Surgical Procedures
chemical_list: D008070:Lipopolysaccharides; D008074:Lipoproteins; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C069172:2,3-bis(palmitoyloxy)-2-propyl-1-palmitoylcysteine; D003545:Cysteine