title: Fibrinogen increases lipopolysaccharide-induced tumor necrosis factor-alpha and interleukin-8 release, and enhances tissue factor activity in monocytes in a modified whole blood system.
abstract: The objective of this study was to investigate the effect of fibrinogen on lipopolysaccharide (LPS)-stimulated blood cells. To this end, a minimum essential blood system was established, reconstituted from washed blood cells and 20% (fibrinogen-free) lepirudin anticoagulated serum in RPMI-1640. Concurrent addition to the system of 1.0-4.0 mg/ml fibrinogen increased LPS-induced tissue factor (TF) activity in the monocytes in a dose-dependent manner. This enhancing effect was, by and large, independent of the LPS concentration (0.5-5.0 ng/ml). Even at the lowest concentration of fibrinogen (1.0 mg/ml), the enhancing effect was quite significant (46-80%) at almost every concentration of LPS tested. Furthermore, LPS-induced release of the two proinflammatory products tumor necrosis factor-alpha and interleukin-8 were also enhanced by added fibrinogen. In conclusion, fibrinogen is capable of enhancing the emergence of certain proinflammatory molecules as well as the procoagulant factor TF, effects that may very well in part be accountable for fibrinogen-related risk of ischemic heart disease and stroke.
authors.affiliation: The authors are with the Department of Biochemistry, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Norway. trinel@fagmed.uit.no
authors.forename: T
authors.initials: T
authors.lastname: Lund
authors.forename: B
authors.initials: B
authors.lastname: Østerud
mesh_terms: D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005340:Fibrinogen / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D013925:Thromboplastin / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen; D006493:Heparin; D013925:Thromboplastin