SUMMARY Specific antibodies to collagen type IV, laminin, and fibronectin were used to localise these proteins by indirect immunofluorescence in frozen sections of normal and fibrotic liver. In normal livers distinct staining was found in basement membranes of blood and lymph vessels, of bile ducts and ductules and around nerve axons. Positive reactions for type IV collagen and fibronectin were also observed in the perisinusoidal space, while hepatocytes and most of the interstitial matrix of portal fields remained unstained. Liver specimens obtained from patients with alcoholic liver disease (fatty liver, hepatitis or cirrhosis) and chronic active hepatitis showed a more intense reaction with the antibodies in the perisinusoidal space including now distinct staining for laminin. These patterns were particularly prominent at borders between fibrotic septa and remnants of parenchyma or pseudolobules. Strong reactions were also found for type IV collagen and fibronectin in the periportal interstitium and in large fibrotic areas. The findings support previous electronmicroscopical and chemical evidence for increased basement membrane production in human liver fibrosis and demonstrate that this may involve different proteins and occur at different anatomical sites.

The expression of alpha 2(I), alpha 1(III) and alpha 1(IV) procollagen mRNA was analyzed in normal and CCl4-induced fibrotic rat liver by in situ hybridization using RNA probes. In normal liver, moderate amounts of alpha 2(I) and alpha 1(III) procollagen transcripts were found in sinusoidal cells, in stromal cells of the portal tracts and in the vicinity of central veins, whereas a1(IV) procollagen gene expression was below the threshold of detection. After 2 weeks of CCl4 treatment, increased transcription of alpha 2(I) and alpha 1(III) procollagen genes was observed in sinusoidal cells. At this stage, alpha 1(IV) procollagen mRNA was detectable in the same cell types and localization as alpha 2(I) and alpha 1(III) procollagen transcripts, although with a weaker signal. After 4 weeks, newly formed fibrous septa showed many cells intensely labeled by alpha 2(I), alpha 1(III) and alpha 1(IV) procollagen probes. Neither in normal liver nor at any stage of fibrosis was any hybridization signal above background observed in hepatocytes. These patterns suggest that in the liver Type I, Type III and Type IV procollagen expression takes place predominantly in nonparenchymal cells. Therefore, hepatocytes do not appear to be significantly involved in procollagen production in this experimental model of liver fibrosis.

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Background-It has recently been shown that humoral antigastric autoreactivities occur in a substantial number of Helicobacter pylori infected patients. Aims-To analyse the relevance of such antigastric autoantibodies for histological and serological parameters of the infection as well as for the clinical course. Methods-Gastric biopsy samples and sera from 126 patients with upper abdominal complaints were investigated for evidence of H pylori infection using histology and serology. Autoantibodies against epitopes in human gastric mucosa were detected by immunohistochemical techniques. Histological and clinical findings of all patients were then correlated with the detection of antigastric autoantibodies. Results-H pylori infection was significantly associated with antigastric autoantibodies reactive with the luminal membrane of the foveolar epithelium and with canalicular structures within parietal cells. The presence of the latter autoantibodies was significantly correlated with the severity of body gastritis, gastric mucosa atrophy, elevated fasting gastrin concentrations, and a decreased ratio of serum pepsinogen I:II. Furthermore the presence of anticanalicular autoantibodies was associated with a greater than twofold reduced prevalence for duodenal ulcer. Conclusion-The data indicate that antigastric autoantibodies play a role in the pathogenesis and outcome of H pylori gastritis, in particular in the development of gastric mucosal atrophy. (Gut 1997; 41: 619-623)