Immunohistochemical localisation of protein tyrosine kinase receptors Tie-1 and Tie-2 in synovial tissue of rheumatoid arthritis: correlation with angiogenesis and synovial proliferation

Objective-To investigate the involvement of Tie-1 and Tie-2, receptor tyros ine kinases required for angiogenesis, in synovial proliferation and angiog enesis of rheumatoid arthritis (RA). Methods-Synovial tissues from 10 patients with RA and three control subject s were analysed by double immunohistochemistry and reverse transcriptase po lymerase chain reaction (RT-PCR). Results-Expression of Tie-1 and Tie-2 was seen in all synovia, but predomin antly in papillary projected portions. In synovial Lining cells, Tie-2 was expressed mainly in the basal layer and frequently colocalised with vimenti n and proliferating cell nuclear antigen (PCNA), whereas Tie-1 was also exp ressed in the superficial layer. In stromal cells, Tie-2 immunoreactivity w as restricted to vimentin positive fibroblast-but not macrophage derived ce lls, whereas Tie-1 expression was not dependent on the phenotype. Tie recep tors were also highly expressed in the endothelium and surrounding pericyte s of capillaries scattered over the papillary proliferated synovium without notable difference in the expression of the two receptors. Furthermore, Ti e positive vessels often overexpressed PCNA. In normal synovia, expression of Tie receptors was restricted to the capillary endothelium. RT-PCR confir med the expression of Tie-1 and Tie-2 in RA synovial tissues and also in th e cultured synoviocytes. Conclusion-The results suggest the possible involvement of overexpressed Ti e-1 and Tie-2 in synovial lining and stromal cells in the pathophysiology o f RA synovitis, probably through distinct mechanisms. Furthermore, expressi on of Tie receptors in actively growing vasculature may reflect the direct involvement of these receptors in angiogenesis and subsequent vascularisati on.