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Microvascular consequences of Kupffer cell modulation in rat liver fibrogenesis
Author(s) -
Vollmar Brigitte,
Siegmund Sören,
Richter Sven,
Menger Michael D.
Publication year - 1999
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199909)189:1<85::aid-path399>3.0.co;2-1
Subject(s) - fibrosis , kupffer cell , chemistry , pathology , hepatic fibrosis , in vivo , carbon tetrachloride , endocrinology , medicine , biology , microbiology and biotechnology , organic chemistry
The process of Ito cell activation, which is thought to be the central pathogenic mechanism in liver fibrogenesis, may involve distinct interactions with Kupffer cells (KCs) mediated by various cytokines and growth factors. The aim of this study was to determine whether targeting KC function using gadolinium chloride (GdCl 3 ) interferes with the manifestation of carbon tetrachloride (CCl 4 )‐induced hepatic fibrosis, placing special emphasis on the process of microvascular remodelling. Using in vivo fluorescence microscopy, characteristic microvascular features of CCl 4 ‐induced liver fibrosis, progressively observed within the 8‐week period of toxin exposure, were the significant reduction in sinusoidal density; the increase of venular vascular space; the perivenular accumulation of Ito cells, with concomitant collagen deposition; and the collapse of parenchymal tissue. GdCl 3 effectively attenuated sinusoidal rarefaction and delayed, but did not prevent, the process of Ito cell activation‐associated collagen deposition. Strikingly, the 8‐week modulation of KC function by GdCl 3 exhibited sustained hepatocellular fatty vacuolation with organ weight increase, liver enzyme release, and bile flow reduction. Thus, GdCl 3 treatment attenuates the hepatic microvascular response, but favours fatty change and only delays the development of liver fibrosis following CCl 4 ‐exposure. Copyright © 1999 John Wiley & Sons, Ltd.