Effects of IC14, an anti-CD14 antibody, on coagulation and fibrinolysis during low-grade endotoxemia in humans.
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.
Verbon
Annelies
A
Department of Infectious Diseases, Tropical Medicine, and AIDS, Academic Medical Center, University of Amsterdam, The Netherlands. A.Verbon@amc.uva.nl
Meijers
Joost C M
JC
Spek
C Arnold
CA
Hack
C Erik
CE
Pribble
John P
JP
Turner
Terence
T
Dekkers
Pascale E P
PE
Axtelle
Tim
T
Levi
Marcel
M
van Deventer
Sander J H
SJ
Reitsma
Pieter H
PH
van der Poll
Tom
T
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
D000911:Antibodies, Monoclonal; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D018180:Thrombomodulin; D013925:Thromboplastin; D025901:Carboxypeptidase B2