title: Effects of IC14, an anti-CD14 antibody, on coagulation and fibrinolysis during low-grade endotoxemia in humans.
abstract: To determine the role of CD14 in lipopolysaccharide (LPS)-induced effects on coagulation and fibrinolysis in humans, 16 healthy subjects received an intravenous injection of LPS preceded by intravenous IC14, a recombinant chimeric monoclonal antibody against human CD14, or placebo. LPS-induced coagulation activation (tissue-factor mRNA in whole blood cells and plasma concentrations of F1+2) was not influenced by IC14, whereas the antibody reduced the increase in thrombin-antithrombin complexes and soluble fibrin. LPS injection also was associated with an early activation of fibrinolysis (plasma concentrations of tissue-type plasminogen activator and plasmin-alpha(2)-antiplasmin complexes), followed by an inhibitory response (plasminogen activator inhibitor type 1), which were attenuated by IC14. Furthermore, LPS reduced thrombin-activatable fibrinolysis-inhibitor antigen levels and increased soluble thrombomodulin levels, which were not influenced by IC14. These results suggest that different hemostatic responses during endotoxemia may proceed via CD14-dependent and -independent pathways.
authors.affiliation: Department of Infectious Diseases, Tropical Medicine, and AIDS, Academic Medical Center, University of Amsterdam, The Netherlands. A.Verbon@amc.uva.nl
authors.forename: Annelies
authors.initials: A
authors.lastname: Verbon
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: C Arnold
authors.initials: CA
authors.lastname: Spek
authors.forename: C Erik
authors.initials: CE
authors.lastname: Hack
authors.forename: John P
authors.initials: JP
authors.lastname: Pribble
authors.forename: Terence
authors.initials: T
authors.lastname: Turner
authors.forename: Pascale E P
authors.initials: PE
authors.lastname: Dekkers
authors.forename: Tim
authors.initials: T
authors.lastname: Axtelle
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Sander J H
authors.initials: SJ
authors.lastname: van Deventer
authors.forename: Pieter H
authors.initials: PH
authors.lastname: Reitsma
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D016466:CHO Cells; D025901:Carboxypeptidase B2 / Q000097:blood; D006224:Cricetinae; D004311:Double-Blind Method; D019446:Endotoxemia / Q000097:blood*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000502:physiology*; D008297:Male; D010976:Platelet Count; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D018180:Thrombomodulin / Q000097:blood; D013925:Thromboplastin / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D018180:Thrombomodulin; D013925:Thromboplastin; D025901:Carboxypeptidase B2