IMMUNOHISTOCHEMICAL PHENOTYPING OF LIVER MACROPHAGES IN NORMAL AND DISEASED HUMAN LIVER

The phenotypical heterogeneity of human liver macrophages was analyzed with monoclonal antibodies that recognize antigens specific for the m onocytemacrophage lineage. Most liver macrophages in normal and diseas ed liver were positive for CD68, whereas fewer matured macrophages wer e detected by 25-F9. Comparative staining of mirror sections revealed some to be doubly positive and others to be singly CD68 positive. Quan titative analysis confirmed the difference, suggesting heterogeneity o f maturation in liver macrophages. Most liver macrophages in the norma l liver were negative for CD14, a receptor for lipopolysaccharide and lipopolysaccharide-binding protein complexes. Liver macrophages in liv er diseases were activated to express CD14 at varying degrees and were involved in the clearance of lipopolysaccharide-lipopolysaccharide-bi nding protein complexes. Fc gamma RI, a receptor for monomeric IgG tha t is involved in antibody-mediated cell cytotoxicity, was negative in the normal liver, but was expressed in liver macrophages at inflammato ry sites (e.g., in piecemeal and focal necrosis) in diseased livers. F c gamma RII was expressed in most liver macrophages, as well as in sin usoidal endothelial cells; Fc gamma RIII was expressed in a smaller nu mber of liver macrophages. Expression of Fc gamma RII and Fc gamma RII I was increased in chronic active hepatitis. These results suggest tha t liver macrophages are heterogeneous in maturation and function and t hat they are activated in liver diseases as shown by the novel express ion of CD14 and Fc gamma RI. The restricted expression of Fc gamma RI indicates that Fc gamma RI-positive macrophages, in cooperation with c ytotoxic T lymphocytes, may play an important role in liver cell injur y through antibody-mediated cell cytotoxicity.