|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1994 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 1993 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Structure of VLA-4 antigen expressed on SLE T cells
In patients with SLE complicated with vasculitis, it has been demonstrated that expressions of not only LFA-1, but also VLA-4 were upregulated. Moreover, the additional high molecular weight band migrating at 180 kD of VLA-4 was obaerved in SLE with vasculitis, whereas 140 kD normal VLA-4 was detected in normal individual and SLE without vasculitis.
Adhesion function and signal transduction via VLA-4 in SLE with vasculitis
Peripheral T cells frpm SLE with vasculitis showed elevated adherence to fibronectin and VCAM-1. After adhesito VLA-4 ligands, ca influx was observed in these T cells, suggesting that this elicited the signal into the cell interior.
Signal transduction through functionally activated VLA-4 in SLE with vasculitis
We next examined the molecular interaction of signal transduction through VLA-4 in these fn these patients in which expression as well as function was upregulated. Given the evidences that intgrins trnasmit signals by binding to cytoskeltal proteins and forming mocal adhesion, talin, one of these cytoskeltal proteins which can binds to cytoplasmic domain of integrin beta chian were observed by Adherent Cell Analyzing System (ACAS) equipped with confocal optical system. We found that focal adhesion and the expression of talin were observed of unstimulated SLE T cells adhered onto fibronectin, whereas those of normal T cells were not. At same time, strong tyrosine-phosphorylation was noted adaround those focal adhesions, suggesting that these signal transduction pathways through intgrins were functionally activated and strongly expressed in T cells from SLE with vasculitis.