Plasma vitronectin polymorphism in normal subjects and patients with
disseminated intravascular coagulation
MG Conlan, BR Tomasini, RL Schultz and DF Mosher
Department of Medicine, University of Wisconsin, Madison 53706.
Vitronectin, also known as serum-spreading factor or S-protein, mediates
cell adhesion and inhibits formation of the membrane-lytic complex of
complement and the rapid inactivation of thrombin by antithrombin III in
the presence of heparin. Vitronectin is normally present in plasma at a
concentration of approximately 300 micrograms/mL. The investigators
quantified plasma vitronectin with an enzyme-linked immunosorbent assay and
visualized reduced and nonreduced vitronectin by immunoblotting after
separation of plasma or serum by sodium dodecyl sulfate-polyacrylamide gel
electrophoresis (SDS-PAGE). The concentration of plasma vitronectin was
markedly reduced in some patients with disseminated intravascular
coagulation, especially in those with liver failure; it was near normal in
patients with metastatic cancer and acute leukemia. Patients with
vitronectin levels less than 40% normal invariably had low fibrinogen and
antithrombin III and a prolonged prothrombin time. In both normal and
patient plasmas there was heterogeneity in the ratio of the 75,000- and
65,000-mol wt polypeptides of reduced vitronectin: 18% had mostly the
75,000-mol wt polypeptide, 59% had roughly equal amounts of the two
polypeptides, and 22% had mostly the 65,000-mol wt polypeptide. This
polymorphism is inherited and appears to be due to two alleles that are
present with approximately equal frequency. The blotting patterns of
vitronectin in reduced and nonreduced plasmas were largely unaltered in
plasma of patients with defibrination syndrome, fibrinolysis, liver
failure, sepsis, metastatic cancer, and acute leukemia. There was no
evidence of fragmentation of vitronectin or formation of the
disulfide-bonded complex of vitronectin and thrombin-antithrombin III that
is found when blood is clotted. Thus these results corroborate in vitro
observations that the liver is the major source of plasma vitronectin,
suggest that vitronectin may become depleted during disseminated
intravascular coagulation, and define a genetic polymorphism of
vitronectin.
Volume 72,
Issue 1,
pp. 185-190,
07/01/1988
Copyright © 1988 by The American Society of Hematology
