To investigate the mechanism of synovial pannus formation in
rheumatoid arthritis, immunohistochemical and immunoelectron microscopic studies with
monoclonal antibodies against the adhesion molecules, CD54 (ICAM-1), CD11a (LFA-1), CDw49a (VLA-1), CDw49b (VLA-2), CDw49c (VLA-3),
Cdw49d (VLA-4) and CDw49e (VLA-5), were carried out to determine the pattern of distribution of these molecules at the rheumatoid synovial cartilage junction. Treatment with anti-ICAM-1 resulted in membrane staining of most of the macrophages and fibroblasts infiltrating the synovial tissue and bordering and pannus-cartilage junction, suggesting the possibility that
ICAM-1 may function to facilitate the adhesion of synovial type A cells bearing
ICAM-1 to type B cells of the pannus.
ICAM-1 positive macrophages and fibroblasts were often found to be in contact with lymphoid cells, suggesting also that a cellular immune reaction occurs in the formation of the pannus. In addition,
VLA-3,
VLA-4 and, particularly,
VLA-5 were the predominant beta 1
integrins expressed by rheumatoid synovial pannus. Sine these three
integrins all function as
fibronectin receptors, it is possible that the
fibronectin-rich environment of the rheumatoid cartilage surface effectively traps pannus cells expressing high levels of these molecules. The
VLA-5 molecule was found in a pericellular and interterritorial matrix distribution in the present study, strongly suggesting that a receptor-
ligand interaction between
VLA-5 and cartilage matrix may occur at the early stage of pannus formation. Furthermore, an increase in beta 1
integrin may be necessary for the growth of the pannus and also for the upregulation of the VLA molecules, leading secondarily to increased attachment.