Immunohistochemical study of extracellular matrix in acute galactosamine hepatitis in rats.
A single injection of D-galactosamine hydrochloride induces acute self-limiting liver disease in rats that morphologically resembles drug-induced hepatitis in human beings. In this immunohistochemical study we examined the localization and expression of the hepatic extracellular matrix components fibronectin, laminin, collagen type I, collagen type III and collagen type IV and of the cell surface receptors (integrins) for fibronectin and laminin. Sections of liver tissue obtained at intervals of 6, 12, 18, 24, 30, 36, 48 and 72 hr and 7 and 21 days after galactosamine administration were immunostained with a panel of polyclonal monospecific antibodies and studied independently by two of us. Fibronectin was the first extracellular matrix component found to be increased, 12 hr after galactosamine injection, followed by collagen type III, and, in a later phase, collagen type IV, type I and laminin. Increased deposition of extracellular matrix was found in areas with liver cell necrosis and along sinusoids. Extracellular matrix immunoreactivity reached a maximum at 36 to 48 hr and decreased thereafter to preinjury levels 3 wk after galactosamine. Immunostaining for the fibronectin and laminin receptors revealed tissue localization identical to that of their ligands. However, the intensity of staining was opposite of that for the extracellular matrix, with a decrease of immunoreactivity after 24 to 48 hr. The observed sequence of changes in hepatic extracellular matrix proteins after galactosamine injection resembles the repair reaction in other tissues and may reflect the particular function that each carries out during the process of liver healing after toxic injury.
Department of Pathology, University of Groningen, The Netherlands.
A M
AM
Jonker
F W
FW
Dijkhuis
A
A
Boes
M J
MJ
Hardonk
J
J
Grond
D000208:Acute Disease; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D005353:Fibronectins / Q000378:metabolism; D005688:Galactosamine; D007150:Immunohistochemistry / Q000379:methods; D007797:Laminin / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D013194:Staining and Labeling
D005353:Fibronectins; D007797:Laminin; D011956:Receptors, Cell Surface; D005688:Galactosamine; D003094:Collagen