Restricted expression of Fc gamma RIII (CD16) in synovium and dermis: implications for tissue targeting in rheumatoid arthritis (RA)

Interactions between immune complexes and immunoglobulin Fc receptors may contribute to inflammation in RA. Previous studies suggested that Fc gamma RIII (CD16) may be preferentially expressed in diseased synovial intima. The distribution of immunoreactive Fc gamma RIII was examined in normal fetal limb tissues, and both normal and selected abnormal samples of adult synovium and skin. In fetal limbs at 10-14 weeks gestation Fc gamma RIII was restricted to synovial intima. In normal adult synovium Fc gamma RIII was restricted to intimal cells. In inflamed synovia differential expression of Fc gamma RIII in the intima was less consistent. In both fetal and adult synovium Fc gamma RIII was largely restricted to cells expressing CD45 (leucocyte common antigen). Staining for Fc gamma RIII was, however, occasionally associated with CD45(-) intimal cells in fetal synovium. In both fetal and adult tissues cell membrane Fc gamma RIII was frequently closely associated with complement decay-accelerating factor (DAF), which is present on intimal fibroblasts and extracellular matrix. Fc gamma RIII expression was minimal in normal forearm dermis, but widespread on CD45(+) cells in skin exposed to mechanical stress. In skin containing rheumatoid nodules, Fc gamma RIII was preferentially expressed on palisading macrophages. These observations indicate that expression of Fc gamma RIII on macrophages may be involved in the susceptibility of connective tissues to immune complex-induced damage in RA. Colocalization of Fc gamma RIII and DAF in synovium may indicate an unrecognized functional interrelationship.