Enhanced expression of the soluble form of E‐selectin attenuates progression of lupus nephritis and vasculitis in MRL/lpr mice. Issue 1 (30th October 2013)

• Record Type: Journal Article
• Authors: Nakatani, Kimihiko; Yoshimoto, Shuhei; Asai, Osamu; Sakan, Hirokazu; Terada, Miho; Saito, Yoshihiko; Nose, Masato; Iwano, Masayuki; Konishi, Noboru
• Is Part Of: Immunity, inflammation and disease. Volume 1:Issue 1 (2013)
• Page Start: 37
• Page End: 46
• Publication Date: 2013-10-30
• Subjects: Lupus -- MRL/lpr mice -- nephritis -- soluble E‐selectin -- vasculitis; Immunology -- Periodicals; Immunity -- Periodicals; Inflammation -- Periodicals; 616.079
• DOI: 10.1002/iid3.6
• Languages: English
• ISSNs: 2050-4527

Abstract

Abstract: 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. Abstract : This study provides the first evidence that E‐selectin plays a critical role in the progression of lupus nephritis and soluble form of E‐selectin proteins may enable development of a new approach to the treatment of lupus nephritis.