Systemic lupus erythematosus (SLE) is a chronic
autoimmune disease that causes inflammatory tissue damage, including
lupus nephritis and
vasculitis. Local generation of adhesion molecules and expression of their
ligands on inflammatory cells appears to contribute to the progression of SLE. We found significantly increased
E-selectin expression in the glomeruli and renal interstitial microvasculature of MRL/MpJ-lpr/lpr (MRL/lpr) lupus model mice. This was accompanied with infiltration of inflammatory cells, especially macrophages and CD8(+) T cells. Similarly, in 21 patients with proliferative
lupus nephritis, there was a significant correlation between renal
E-selectin levels and macrophage and CD8(+) T cell infiltration in the affected kidneys. By contrast, in transgenic MRL/lpr mice exhibiting elevated levels of circulating soluble
E-selectin (sE-
selectin)
protein, which competitively inhibits E- and
P-selectin-mediated extravasation of inflammatory cells, the progression of
lupus nephritis and
vasculitis was significantly suppressed and survival was significantly prolonged. This improvement was accompanied by significant reductions in renal infiltration by macrophages and CD8(+) T cells. These results suggest that
E-selectin plays a crucial role in
lupus nephritis and
vasculitis by mediating renal infiltration of inflammatory cells, and that because it inhibits this process, sE-
selectin could potentially serve as an effective treatment for
lupus nephritis and
vasculitis.