Phenotypic modulation of perisinusoidal cells following acute liver injury: a quantitative analysis.
Expression of the alpha-(smooth muscle) isoform of actin (alpha-SMA) by non-parenchymal cells in rat liver was studied following induction of acute liver injury using a single sublethal dose of carbon tetrachloride (CCl4). In normal liver, alpha-SMA immunoreactivity was identified in the smooth muscle cells of hepatic arteries and in the walls of portal and hepatic vein branches. Occasional alpha-SMA-containing stellate shaped cells were found in acinar zone 3 but most perisinusoidal cells (PSCs) did not express this protein. In CCl4-treated animals, there was an increase in the number of immunoreactive cells in perivenular zones, reaching a peak at day 3 following exposure to the toxin. These cells were morphologically identical to desmin-positive PSCs and the kinetics of the responses of alpha-SMA-positive and desmin-positive cells were similar. In en face labelling experiments, evidence of co-expression of alpha-SMA and desmin by non-parenchymal cells was obtained, although some desmin-positive PSCs did not appear to express alpha-SMA. These results suggest that PSCs rapidly undergo phenotypic modulation in response to acute liver injury with acquisition of alpha-SMA expression. It is proposed that these phenotypic changes coincide with functional alterations, such activated 'myofibroblast-like' cells being responsible for the enhanced matrix protein synthesis necessary for tissue repair.
Johnson
S J
SJ
Division of Pathology, School of Pathological Sciences, University of Newcastle upon Tyne, Royal Victoria Infirmary, UK.
Hines
J E
JE
Burt
A D
AD
D000199:Actins / Q000032:analysis*; D000208:Acute Disease; D000818:Animals; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury; D003893:Desmin / Q000032:analysis; D007124:Immunoenzyme Techniques; D008099:Liver / Q000737:chemistry / Q000473:pathology*; D008107:Liver Diseases / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000199:Actins; D003893:Desmin; D002251:Carbon Tetrachloride