von Willebrand factor release induced by endotoxin.
In vitro von Willebrand factor is released from endothelial cells by a variety of stimuli. These studies have provided information on the synthesis, multimeric organization, sites of storage, and release of von Willebrand factor. We have administered endotoxin (Escherichia coli, 4 ng/kg) intravenously to 11 normal volunteers and have followed changes in levels of factor VIII, von Willebrand factor antigen, von Willebrand factor activity (ristocetin cofactor assay), and the multimeric organization of von Willebrand factor. Within 2 hours after injection, the levels of factor VIII, von Willebrand factor antigen, and von Willebrand factor activity rose significantly compared with the preinjection values (p less than 0.001, p less than 0.005, and p less than 0.001, respectively). The levels peaked 4 to 6 hours after the endotoxin injection. The mean peak values of von Willebrand factor antigen and activity were 4.67 microns/ml and 4.62 microns/ml, respectively. The factor VIII level rose to a mean of 2.87 microns/ml. Forty-eight hours after the administration of endotoxin, the von Willebrand factor antigen and activity levels remained significantly elevated (2.62 micrograms/ml and 2.20 microns/ml, respectively), but by 24 hours, the factor VIII level was not significantly elevated (1.47 microns/ml). After endotoxin administration, the agarose gel electrophoresis of von Willebrand factor demonstrated an increase in the largest von Willebrand factor multimers normally present and the appearance of von Willebrand factor multimers larger than those normally present in plasma. The largest von Willebrand factor multimers were present for 2 to 4 hours after the administration of endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)
Gralnick
H R
HR
Clinical Pathology Department, National Institutes of Health, Bethesda, MD 20892.
McKeown
L P
LP
Wilson
O M
OM
Williams
S B
SB
Elin
R J
RJ
D000328:Adult; D000941:Antigens / Q000032:analysis; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D005169:Factor VIII / Q000032:analysis; D006801:Humans; D008297:Male; D014841:von Willebrand Factor / Q000378:metabolism*
D000941:Antigens; D004731:Endotoxins; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; D005169:Factor VIII; D003894:Deamino Arginine Vasopressin