Mig, GRO alpha and RANTES messenger RNA expression in lining layer, infiltrates and different leucocyte populations of synovial tissue from patients with rheumatoid arthritis, psoriatic arthritis and osteoarthritis.

Abstract

To investigate lymphocyte and monocyte recruitment-specific chemokine expression in synovial tissues from patients with rheumatoid arthritis (RA), psoriatic arthritis (PA) and osteoarthritis (OA), synovial membranes and cytocentrifuge preparations of 7 RA, 8 PA and 10 OA patients were examined by in situ hybridisation with antisense probes of Mig, GRO alpha and RANTES and by immunohistochemistry. Patients' local disease activity (swelling and tenderness) in order to was graded and histological evaluation was performed compare these data with their chemokine expression profiles. Mig and RANTES hybridisation signals were detected in the synovial lining layer and in cellular infiltrates, whereas GRO alpha expression was localised exclusively in the lining layer of PA and RA. Cytological analysis revealed Mig and GRO alpha mRNA mainly in monocytic cells expressing KIM6, while RANTES mRNA was demonstrated predominantly in lymphocytic cells expressing CD3. In OA synovial membranes, significantly fewer hybridisation signals were present than in RA and PA synovial membranes. Patients with PA and RA had mild to severe local disease activity, whereas OA patients showed only mild disease activity. Histologically, PA and RA inflammatory scores ranged from 1 to 5, while OA synovium was consistently graded 1. Therefore, we conclude that the differential expression of Mig, GRO alpha and RANTES in resident and in inflammatory cells has an important role in regulating leucocyte traffic in inflammatory arthropathies. The diverse leucocyte specificity of Mig, GRO alpha and RANTES may thus regulate the recruitment of different leucocyte populations, as detected in PA and RA. Therefore, the pattern of cellular infiltration in human synovitis and the corresponding clinical signs of inflammation basically reflect the localisation and expression intensity of chemokines, which may be an important target for future disease modulation.