Combined anticoagulant and antiselectin treatments prevent lethal intravascular coagulation.
Widespread microvascular injury followed by vessel obstruction may lead to disseminated intravascular coagulation (DIC). We describe a murine model wherein leukocytes interacting with inflamed microvessels in vivo are activated by antibodies. Treatment of tumor necrosis factor alpha (TNF-alpha)-primed mice with anti-Ly-6G antibodies reproduced many of the features of septic or traumatic shock including microvessel obstruction and coagulation, severe vasculitis, respiratory difficulties, and vascular leakage. Mice lacking either E-selectin or P-selectin were protected from this reaction as were animals treated with a combination of either selectin-blocking antibodies and heparin or a selectin antagonist plus heparin. Combined blockade of leukocyte/platelet adhesion and coagulation may provide convincing protection in DIC.
Norman
Keith E
KE
Cardiovascular Research Group, Division of Clinical Sciences (North), University of Sheffield, Sheffield, United Kingdom. k.norman@shef.ac.uk
Cotter
Matthew J
MJ
Stewart
James B
JB
Abbitt
Kate B
KB
Ali
Majid
M
Wagner
Bart E
BE
Wallace
William A H
WA
Forlow
S Bradley
SB
Hellewell
Paul G
PG
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology*; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology*; D000950:Antigens, Ly / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000473:pathology; D019087:Selectins / Q000235:genetics / Q000276:immunology*; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects
D000906:Antibodies; D000925:Anticoagulants; D000950:Antigens, Ly; D019087:Selectins; D014409:Tumor Necrosis Factor-alpha; D006493:Heparin