IMMUNOHISTOCHEMICAL STUDY OF ADHESION MOLECULES IN LIVER INFLAMMATION

Using monoclonal antibodies and in situ immunohistochemistry, we studied the distribution of “accessory” adhesion molecules (i.e., intercellular adhesion molecule‐1 and leukocyte function–associated antigen‐3) in 114 liver biopsy specimens with various inflammatory liver diseases and in 12 control liver biopsy samples without inflammation. The distribution of these adhesion molecules was compared with the presence on inflammatory cells of their natural ligands, lymphocyte function–associated antigen‐1 and cluster of differentiation antigen‐2, respectively. In normal liver, intercellular adhesion molecule‐1 and leukocyte function–associated antigen‐3 reacted weakly with sinusoidal lining cells, portal vessel endothelium and scattered mononuclear inflammatory cells, whereas hepatocytes were constantly negative. In contrast, all 114 biopsy samples of acute or chronic liver diseases revealed strong expression of intercellular adhesion molecule‐1 and leukocyte function–associated antigen‐3 on sinusoidal lining cells and on hepatocytes in areas of inflammation. Hepatocellular membrane positivity resulted in a “honeycomb pattern” of staining, which was panacinar in acute hepatitis and focal in chronic persistent or aggressive hepatitis. In various other chronic liver diseases, a multifocal periportal and intraacinar honeycomb pattern was detected. In all cases, a close topographical correlation was found between hepatocellular expression of intercellular adhesion molecule‐1 and leukocyte function–associated antigen‐3 on one hand and the presence of inflammatory cells expressing lymphocyte function–associated antigen‐1 and cluster of differentiation antigen‐2 on the other. These data suggest that in inflammatory liver diseases adhesion between hepatocytes and inflammatory cells is mediated by two different pathways of cellular interaction, involving intercellular adhesion molecule‐1/lymphocyte function–associated antigen‐1 and leukocyte function–associated antigen‐3/cluster of differentiation antigen‐2. This may result in increased adherence and may facilitate antigen presentation to and activation of inflammatory cells. In this way, hepatocytes may play an active immunoregulatory role in the recruitment and retention of inflammatory cells during an immune response. (HEPATOLOGY 1990;12:59–65). Copyright © 1990 American Association for the Study of Liver Diseases