Enhanced expression of the soluble form of E-selectin attenuates progression of lupus nephritis and vasculitis in MRL/lpr mice.
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.
Department of Pathology, Nara Medical University Kashihara, Nara, Japan ; First Department of Internal Medicine, Nara Medical University Kashihara, Nara, Japan.
Kimihiko
K
Nakatani
First Department of Internal Medicine, Nara Medical University Kashihara, Nara, Japan.
Shuhei
S
Yoshimoto
First Department of Internal Medicine, Nara Medical University Kashihara, Nara, Japan.
Osamu
O
Asai
First Department of Internal Medicine, Nara Medical University Kashihara, Nara, Japan.
Hirokazu
H
Sakan
Division of Pathogenomics, Department of Pathology, Ehime University Graduate School of Medicine To-on, Ehime, Japan.
Miho
M
Terada
First Department of Internal Medicine, Nara Medical University Kashihara, Nara, Japan.
Yoshihiko
Y
Saito
Division of Pathogenomics, Department of Pathology, Ehime University Graduate School of Medicine To-on, Ehime, Japan.
Masato
M
Nose
First Department of Internal Medicine, Nara Medical University Kashihara, Nara, Japan ; Division of Nephrology, Department of General Medicine, Faculty of Medical Sciences, University of Fukui Yoshida-gun, Fukui, Japan.
Masayuki
M
Iwano
Department of Pathology, Nara Medical University Kashihara, Nara, Japan.
Noboru
N
Konishi
Lupus; MRL/lpr mice; nephritis; soluble E-selectin; vasculitis