Endothelial adhesion molecules in glomerular lesions: association with their severity and diversity in lupus models.
BACKGROUND
To clarify whether vascular endothelial adhesion molecules in glomeruli might contribute to the severity and diversity of glomerular lesions in lupus nephritis, their expression in lupus models was analyzed.


METHODS
The expression levels of E- and P-selectin and vascular cell adhesion molecule-1 (VCAM-1) in glomeruli of different histopathologic grades of MRL/MpJ-lpr/lpr (MRL/lpr) lupus mice was studied using laser-capture microdissection of the glomeruli, followed by reverse transcription-polymerase chain reaction (RT-PCR) analysis. The glomerular lesions in SCID mice injected with the 2B11.3 and 7B6.8 clones, which are derived from an MRL/lpr mouse and induce endocapillary proliferative and wire loop type of glomerular lesions, respectively, were analyzed. To investigate the effect of a soluble form of E-selectin (sE-selectin) on the development of glomerular lesions, sE-selectin-producing L cells were prepared by transfection of the cDNA encoding sE-selectin and injected into SCID mice.


RESULTS
The glomeruli in MRL/lpr mice showed increased expression of these adhesion molecules, corresponding to the severity of the glomerular lesions. The endocapillary proliferative type lesions in SCID mice induced by the 2B11.3 clone showed significantly increased expression of the adhesion molecules, especially E-selectin and P-selectin, but the wire loop type lesion induced by the 7B6.8 clone expressed only VCAM-1. Formation of the endocapillary proliferative type lesions induced by the 2B11.3 clone was markedly prevented in association with elevation of the serum level of sE-selectin produced by the tansfected L cells.


CONCLUSIONS
The severity and diversity of the histopathology of lupus nephritis are partially associated with the expression of vascular endothelial adhesion molecules in glomeruli.
Nakatani
Kimihiko
K
Department of Pathology and Department of Internal Medicine, Ehime University School of Medicine, Onsen-gun, Ehime, Japan.
Fujii
Hiroshi
H
Hasegawa
Hitoshi
H
Terada
Miho
M
Arita
Norimasa
N
Ito
Mitsuko R
MR
Ono
Masao
M
Takahashi
Satoru
S
Saiga
Kan
K
Yoshimoto
Shuhei
S
Iwano
Masayuki
M
Shiiki
Hideo
H
Saito
Yoshihiko
Y
Nose
Masato
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D019040:E-Selectin / Q000096:biosynthesis / Q000737:chemistry; D042783:Endothelial Cells / Q000378:metabolism*; D007674:Kidney Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology*; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D016513:Mice, SCID; D019007:P-Selectin / Q000378:metabolism; D012720:Severity of Illness Index; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1