HETEROGENEITY OF LIVER-CELLS EXPRESSING PROCOLLAGEN TYPE-I AND TYPE-IV IN-VIVO

The extracellular matrix of fibrotic liver is predominantly produced b y mesenchymal cells, the in vivo phenotype of which is poorly defined. We report on the application of combined immunohistology and in situ hybridization with [S-35]-labeled alpha 1(I) and alpha 1(IV) procollag en RNA probes. In CCl4-treated rats, all alpha 1(I) procollagen-produc ing cells were vimentin positive but cytokeratin negative; over 90% ex pressed desmin, a marker of rat liver stellate cells. alpha 1(I) Proco llagen-expressing, desmin-negative cells were confined to portal tract and perivascular stroma. Similarly, alpha 1(I) procollagen gene trans cripts were, in all instances, colocalized with vimentin in human live r. In fibrotic specimens, over 70% of these cells expressed alpha-acti n. Antibodies against epithelial, endothelial, and Kupffer cells, gran ulocytes, and lymphocytes did not react with alpha 1(I) procollagen RN A-expressing cells. Localization, morphology, and immunophenotype of a lpha 1(I) procollagen-expressing cells indicated stellate cells and po rtal/vascular fibroblasts, but not epithelial cells, to be sources of hepatic interstitial collagen. However, most alpha 1(IV)-expressing hu man Liver cells were identified as endothelial cells, the remaining ce lls were (myo-)fibroblastic and bile duct epithelial cells, but not he patocytes. This indicates synthesis of procollagen type IV from both s ides of the basement membrane and suggests an active participation of endothelial cells in the process of sinusoidal capillarization.