title: Comparison of the capacity of rhTNF-alpha and Escherichia coli to induce procoagulant activity by baboon mononuclear cells in vivo and in vitro.
abstract: The procoagulant activity of mononuclear cells (MNCs) may play an important role in the disseminated intravascular coagulation seen in septic shock. This study compares the capacity of Escherichia coli (E. coli) and recombinant human TNF-alpha (rhTNF-alpha) to induce procoagulant activity by baboon MNCs. In vivo studies showed that MNC procoagulant activity was significantly increased at T + 120 min after LD100 E. coli infusion into baboons. Most of this procoagulant activity was attributable to tissue factor. In contrast, a bolus infusion of rhTNF-alpha (150 micrograms/kg) and a monoclonal antibody to activated protein C (2 mg/kg) did not induce any increase of MNC procoagulant activity at T + 120 min even though the plasma TNF-alpha level was 10 times higher than that seen following infusion of E. coli. In vitro studies showed that E. coli at concentrations comparable to that observed in the vivo study and LPS at a concentration of 2.5 ng/mL induced more intense tissue factor expression by both human and baboon monocytes than rhTNF-alpha in the concentrations ranging from 10 to 1,000 ng/mL. These results suggest that TNF-alpha alone is not sufficient to induced noticeable MNC procoagulant activity, at least, in the early stage of this septic shock model.
authors.affiliation: Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
authors.forename: A
authors.initials: A
authors.lastname: Li
authors.forename: A C
authors.initials: AC
authors.lastname: Chang
authors.forename: G T
authors.initials: GT
authors.lastname: Peer
authors.forename: L B
authors.initials: LB
authors.lastname: Hinshaw
authors.forename: F B
authors.initials: FB
authors.lastname: Taylor
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003029:Coagulants / Q000494:pharmacology; D004211:Disseminated Intravascular Coagulation / Q000139:chemically induced / Q000503:physiopathology*; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000401:mortality; D005340:Fibrinogen / Q000032:analysis / Q000187:drug effects; D006801:Humans; D007928:Lethal Dose 50; D007962:Leukocytes / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D010215:Papio; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy; D013925:Thromboplastin / Q000096:biosynthesis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000494:pharmacology*
chemical_list: D003029:Coagulants; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen; D013925:Thromboplastin