Liver collagen synthesis in murine schistosomiasis.

Abstract

A B S T R A C T Collagen synthesis was measured in liver slices obtained from mice with hepatosplenic schistosomiasis. Enlarged fibrotic livers from these mice contained 20 times more collagen than normal. This model of hepatic fibrosis results from an inflammatory granulomatous host response to Schistosoma mansoni ova in portal tracts, rather than from direct liver cell injury as with carbon tetrachloride-induced liver fibrosis. Collagen synthesis, as measured by the formation of labeled protein-bound hydroxyproline, occurred in granulomas isolated from fibrotic livers. Labeled collagen that cochromatographed with type I collagen was extracted with neutral salt solution from liver slices incubated with labeled proline. The free proline pool of the liver was doubled in infected mice; coordinately, liver slices from these animals showed maximal collagen production when the concentration of free proline in the medium was raised to 0.4 mM, the same level measured in the fibrotic livers. Under such conditions, collagen synthesis was at a rate equivalent to the formation of 5.4 nmol of protein-bound hydroxyproline per g liver in 6 h.In comparative incubations in medium containing 0.2 mM proline, fibrotic liver slices produced 16-fold more collagen than normal slices. The proline analogue, L-azetidine 2-carboxylic acid, effectively inhibited synthesis of labeled collagen by fibrotic liver slices. These studies show the synthesis of collagen in a reproducible animal model of the most prevalent form of human liver fibrosis. Definitition of the controlling factors in this system is of interest for the general problem of fibrosis produced by immunological responses.

Malnutrition and hepatic fibrosis in murine schistosomiasis

“…Hepatic fibrosis in S. mansoni infected mice is mainly associated with the circumoval granulomas (Dunn et al 1977), although some portal fibrosis not associated with granulomas is also present (Cheever 1965).…”

Immunopathology of Schistosoma mansoni infection

“…Analysis of the fibrotic process in humans has yielded some limited but interesting data. Measurement of collagen content and rate of collagen synthesis in fibrotic livers showed a 5-to 40-fold increase over that of normal livers (116,117). In liver sections, immunocytochemical methods detected type I, type III, and B collagens in portal spaces, fibrous septa, and granulomas (30).…”

“…In mice, hepatic fibrosis is mostly associated with circumoval granulomas (15,119). It is still controversial whether classical Symmers' fibrosis develops during mild prolonged infection in this species (15).…”

The feasibility of MS and advanced data processing for monitoring Schistosoma mansoni infection

“…Previous studies showed that collagen biosynthesis is adapted in response to Schistosoma infection. Because the classical tissue response to deposited ova is granulomatous [20] it is possible that individuals suffering from S. mansoni develop dense deposits of collagen and glycosaminoglycans to form granulomas [21,22]. The collagen isotype profile described for these granulomas was an increased type III and decreased type I collagen.…”