COLLAGEN-XVIII IS LOCALIZED IN SINUSOIDS AND BASEMENT-MEMBRANE ZONES AND EXPRESSED BY HEPATOCYTES AND ACTIVATED STELLATE CELLS IN FIBROTIC HUMAN LIVER

Type XVIII collagen is a recently discovered nonfibrillar collagen ass ociated with basement membranes in mice and expressed at high levels i n human liver We studied the origin, distribution, and RNA levels of t ype XVIII collagen in normal and fibrotic human livers by in situ hybr idization, immunohistochemistry, and Northern and dot blots and compar ed procollagen alpha 1 (XVIII) RNA levels with those of procollagen al pha 1(IV) and laminin gamma 1, the two major components of liver basem ent membranes. In normal liver, type XVIII collagen was heavily deposi ted in perisinusoidal spaces and basement membrane zones. The major so urce of type XVIII collagen was hepatocytes and, to a lesser extent, e ndothelial, biliary epithelial, and vascular smooth muscle cells and p eripheral nerves. In cirrhosis, type XVIII collagen formed a thick dep osit along capillarized sinusoids. Grain counts after in situ hybridiz ation showed myofibroblasts to increase their expression 13-fold in ac tive and twofold in quiescent fibrosis,whereas hepatocytes increased t heir expression only twofold in both active and quiescent fibrosis. Ac tivated stellate cells in vitro expressed type XVIII collagen at high levels. These data indicate that type XVIII collagen is a component of the perisinusoidal space and is associated with basement membrane rem odeling. Hepatocytes and activated stellate cells are important source s of type XVIII collagen in normal and fibrotic liver respectively, wh ich suggests tissue-specific regulation of its expression.