Expression of CD147 on monocytes/macrophages in rheumatoid arthritis: its potential role in monocyte accumulation and matrix metalloproteinase production

Monocytes/macrophages are known to play an important role in the pathogenesis of rheumatoid arthritis (RA). The number of monocytes/macrophages infiltrating into the rheumatoid synovium correlates with the extent of the inflammation in synovial tissues [1]. At the cartilage-pannus junction, macrophages, together with fibroblasts and endothelial cells, are important sources of matrix metalloproteinases (MMPs), which have been demonstrated to be involved in the process of cartilage and subchondral bone degradation [2,3]. The potential of macrophages to degrade cartilage matrix components may be modest, however, compared with that of synovial fibroblasts, which are thought to be possibly one of the principle cells involved in effecting the destructive response [4,5]. Thus, rather than the primary effector of tissue destruction, macrophages may act as an amplifier of the pathogenetic cascade, especially via activation of fibroblasts by molecules such as IL-1 and tumor necrosis factor (TNF)-alpha. Other molecules, such as CD147, also participate in this process and may play important roles in RA pathogenesis, but very few reports have been presented on their precise functions.CD147 (also known as extracellular MMP inducer (EMMPRIN), basigin, tumor cell-derived collagenase stimulatory factor, human leukocyte activation-associated M6 antigen, or HAb18G) is a highly glycosylated immunoglobulin superfamily transmembrane protein [6,7]. It was initially identified on the surface of human cancer cells and has been proven to stimulate the adjacent stromal cells to produce several MMPs, including MMP-1, MMP-2, MMP-3, membrane type 1 MMP (MT1-MMP) and MT2-MMP [8-10]. Cellular expression analysis using the monoclonal antibodies from an international workshop on HLA indicates that CD147 is broadly expressed on haemopoietic and non-haemopoietic cell lines [11]. The CD147 expressed by monocytes/macrophages may similarly induce MMP production by fibroblasts and play an essential role i