Characterization of the molecular forms of fibronectin in fulminant hepatic failure

Abstract

The plasma levels of the opsonic glycoprotein fibronectin are decreased in patients with fulminant hepatic failure, which may be an important factor in their impaired host-defense. Twenty-nine patients in fulminant hepatic failure were studied on admission, and the mean fibronectin level in Grade 0-2 encephalopathy was 82 micrograms per ml (range = 0 to 150) and in Grade 3-4 encephalopathy 61 micrograms per ml (range = 5 to 158) as compared to normal controls (268 micrograms per ml, range = 178 to 380, n = 62). No fibronectin degradation products could be detected in fulminant hepatic failure plasma by sodium dodecyl sulfate-gel electrophoresis on a polyacrylamide gradient (5 to 15%) followed by immunoblotting onto nitrocellulose with detection using a rabbit antihuman fibronectin antiserum visualized with a peroxidase conjugate. The plasma levels of the marker proteolytic enzyme cathepsin D were significantly elevated in fulminant hepatic failure (120 +/- 31 mU per ml per hr) as compared to the normal controls (18 +/- 2.1 mU per ml per hr, n = 10, p less than 0.01). Cross-immunoelectrophoresis of fulminant hepatic failure plasma for fibronectin on agarose plates gave an additional slower migrating peak in 15 of the 29 patients, as well as that of fibronectin, which corresponded to the fibronectin complex reported by other workers in leukemia. An intermediate gel containing antihuman fibrinogen demonstrated fibrinogen to be one component of this complex. Binding of other substances to fibronectin will reduce its apparent biological activity and may be the result of their lack of clearance by the damaged liver.

Fibronectin and liver disease

“…The studies of Almasio et al (19) extend previous observations of plasma fibronectin in fulminant hepatic failure. The levels of fibronectin, determined immunologically, were invariably low, often to 4 0 % of normal.…”

“…The two papers (19,20) appearing elsewhere in this issue represent significant advances in this regard.…”

“…A major hurdle in the elucidation of the clinical and pathophysiological importance of low plasma fibronectin concentration is the establishment of experimental models and/or identification of clinical conditions in which fibronectin concentration is reproducibly low and remains so over a sustained period of time. The two papers (19,20) appearing elsewhere in this issue represent significant advances in this regard.…”