Association between E-selectin expression and histopathological modification of glomerular lesions by non-nephritogenic IgM antibodies in experimental lupus nephritis

Abstract

Objective. To examine the role played by E-selectin in bystander IgM-mediated modification of glomerular lesions in experimental lupus nephritis.

Methods. Experimental lupus SCID mice were induced by an intraperitoneal injection of clone 7B6.8, which was derived from a MRL/lpr mouse and shown to induce wire-loop type glomerular lesions. Mice were subsequently administered clone Sp6, a non-nephritogenic IgM antibody- producing hybridoma. E-selectin expression was then evaluated in glomeruli showing histopathological conversion of lesions from wire-loop-like to a cell-proliferative form. We also investigated the effects of a circulating soluble form of E-selectin (sE-selectin) on the modification of glomerular lesions in this lupus model.

Results. In experimental lupus mice, glomerular E-selectin expression significantly increased during the conversion from wire-loop-like glomerular lesions to a cell-proliferative type mediated by a non-nephritogenic bystander IgM antibody in presence of a nephritogenic antibody. Intraglomerular infiltration of CD68 + macrophages correlated significantly with the glomerular level of E-selectin expression. In addition, overexpression of circulating sE-selectin significantly suppressed conversion to cell-proliferative glomerular lesions and glomerular macrophage infiltration in these lupus model mice.

Conclusions. The histopathological modification of lupus nephritis by non-nephritogenic bystander IgM antibodies is associated in part with glomerular E-selectin expression.

Keywords:

• E-selectin
• Histopathology
• IgM antibody
• Lupus nephritis
• Nephritogenic antibody

Acknowledgements

The authors are indebted to Mses. Aya Asano, Nobuko Fujita and Miyako Sakaida of Nara Medical University for their excellent technical assistance.

Conflict of interest

None.