QUANTITATIVE-ANALYSIS OF MACROPHAGES AND PERISINUSOIDAL CELLS IN PRIMARY BILIARY-CIRRHOSIS

Immunohistochemistry and image analysis were used to quantify alterati ons in the Kupffer cell and 'activated' perisinusoidal cell population s in the different stages of primary biliary cirrhosis. Anti-CD68 macr ophage antibodies were used to detect Kupffer cells, and anti-alpha-sm ooth muscle actin (alpha-SMA), PR 2D3 and anti-desmin antibodies to de tect perisinusoidal cells. Liver biopsy material was available from 26 patients with primary biliary cirrhosis and 23 patients with histolog ically normal liver. Increased Kupffer cell numbers were observed in p eriportal/periseptal zones of stage 3 primary biliary cirrhosis (n = 9 ), and in random parenchymal areas of stage 3 and stage 4 cases. Signi ficantly increased 'activated' perisinusoidal cell numbers were seen o nly in periportal/periseptal zones of stage 3 and stage 4 primary bili ary cirrhosis. Neither Kupffer cell nor perisinusoidal cell numbers al tered significantly in stage 1 and 2 primary biliary cirrhosis (n = 6) . PR 2D3 positivity and increased alpha-SMA immunoreactivity by perisi nusoidal cells in primary biliary cirrhosis support myofibroblastic di fferentiation of these cells. Human perisinusoidal cells, unlike their rodent counterparts, did not express desmin in primary biliary cirrho sis or control liver. Kupffer cell and 'activated' perisinusoidal cell accumulation in periportal/periseptal zones of the precirrhotic and c irrhotic primary biliary cirrhosis liver support the concept of Kupffe r cell-mediated stimulation of perisinusoidal cells. Furthermore, thes e findings indicate that Kupffer cell-perisinusoidal interactions play an important role in the development of liver fibrosis and cirrhosis in primary biliary cirrhosis.