IMMUNOHISTOLOGICAL AND FUNCTIONAL-ANALYSIS OF ADHESION MOLECULE EXPRESSION IN THE RHEUMATOID SYNOVIAL LINING LAYER - IMPLICATIONS FOR SYNOVIAL LINING CELL DESTRUCTION

Objective. It has previously been shown that the adhesion of lymphocyt es to microvascular endothelium mediates lymphocyte extravasation with in inflamed synovium. After passing the endothelial barrier, binding o f lymphocytes to matrix proteins and synovial lining cells may further lead to synovial membrane hyperplasia and subsequent cartilage destru ction. Thus, we have explored the molecular basis of T cell-synovial l ining cell interaction in the synovial membrane of patients with rheum atoid arthritis (RA). Methods. Using an immunohistochemical staining t echnique and an in vitro frozen section assay we studied the expressio n and the role of several adhesion molecules in T lymphocyte-synovial lining cell interaction in the inflamed synovial membrane. Results. In RA the macrophage-like (type A) synovial lining cells express high le vels of intercellular adhesion molecule 1 [ICAM-1 (CD54)], whereas the fibroblast-like (type B) synovial lining cells predominantly express vascular cell adhesion molecule 1 (VCAM-1), in addition to moderate le vels of ICAM-1. Both cell types express low levels of fibronectin. Uns timulated and anti-CD3 stimulated peripheral blood T cells bear the re spective ligands lymphocyte function associated antigen 1 [LFA-I (CD18 /11a)], and very late antigen 4 and 5 [VLA-4 (CD29/49d) and VLA-5 (CD2 9/49e)]. T lymphocytes predominantly bound to type B synovial lining c ells. Inhibition studies with monoclonal antibodies revealed that this binding involves the VLA-4/VCAM-1 and VLA-5/fibronectin (FN), but not the VLA-4/CS1 pathway. LFA-1 is also involved in this interaction via its ligand ICAM-1. Conclusion. These results show that the molecular basis of T lymphocyte binding to rheumatoid synovial lining cells is d ifferent from that described for T lymphocyte binding to synovial memb rane vascular endothelium which involves the VLA-4/VCAM-1 and VLA-4/CS -1 pathways, but not the LFA-1/ICAM-1 pathway.