Macrophages express granzyme B in the lesion areas of atherosclerosis and rheumatoid arthritis

Abstract

Granzyme B is a major mediator of the cytotoxic immune response by inducing target cell death when internalized in the presence of perforin. Recently, several studies have focused on another role of granzyme B, which is extracellular matrix (ECM) remodeling through the degradation of ECM proteins. In order to investigate the expression pattern of granzyme B in the lesion areas of atherosclerosis and rheumatoid arthritis, we performed immunohistochemistry and in situ hybridization analyses using human atherosclerotic plaques and the synovial tissues of rheumatoid arthritic- and osteoarthritic-joints. In atherosclerotic plaques, granzyme B was expressed by macrophages in areas such as the boundary regions between media and intima, areas around necrotic cores, and in shoulder regions. In the synovial tissues of rheumatoid arthritic-joints, the expression of granzyme B was strongly observed in the lining layers where the majority of cells are macrophages and also in perivascular areas where macrophages and a small number of lymphocytes were mixed to form diffuse cellular aggregates. Granzyme B-positive cells were not detected in osteoarthritic synovium. Furthermore, the expression of granzyme B has been induced in the human macrophage cell line, THP-1, by ECM proteins or agents which induce macrophage differentiation. These observations indicate that macrophages should be added to the list of cell types that express granzyme B in human inflammatory diseases and that granzyme B may play a role in macrophage functions that are associated with disease progression.