Portal tract macrophages are increased in alcoholic liver disease

Previous studies indicated decreased numbers and depressed clearance function of hepatic macrophages in alcoholic liver disease (ALD). We examined hepatic macrophages by immunohistochemical techniques in 45 liver biopsies from patients with a spectrum of ALD and compared them with 20 histologically normal biopsies from non-alcoholic patients. Antisera against lysozyme, alpha 1-antitrypsin (alpha 1AT) and a cytoplasmic molecule on macrophages (MAC-387) were used and the number of positively staining hepatic sinusoidal macrophages and portal tract macrophages assessed separately. Portal tract macrophage numbers were increased with all three markers in biopsies exhibiting only fatty change (P less than 0.05) and with MAC-387 in all ALD groups. In agreement with previous studies, lysozyme positive hepatic sinusoidal macrophages were decreased in all ALD groups. However, the other markers did not show any significant decrease and MAC-387 positive macrophages were increased in livers with cirrhosis plus hepatitis (P less than 0.01). The use of three markers revealed phenotypic heterogeneity of hepatic macrophages with antibodies to lysozyme and alpha 1 AT staining more hepatic sinusoidal macrophages than MAC-387, but MAC-387 and anti-lysozyme staining more portal tract macrophages than anti-alpha 1AT. Since hepatic macrophages appear to be heterogeneous and capable of diverse functions including the release of cytotoxic mediators, the finding of increased numbers, even in early ALD, suggests they may contribute to the increased numbers, even in early ALD, suggests they may contribute to the tissue damage.