Adhesion molecule expression precedes brain damages of lupus-prone mice and correlates with kidney pathology.
Central nervous system (CNS) involvement is a frequent and potentially life-threatening complication in systemic lupus erythematosus (SLE) yet the mechanisms of organ damage remain poorly understood. Upregulation of cellular adhesion molecules in kidney and other organs has been implicated in the expression of inflammation and tissue injury, but the relation between kidney pathology and altered brain function has not been studied. We therefore analyzed the expression of cellular adhesion molecules ICAM-1, VCAM-1, and E-selectin in brains from 6 to 14week old MRL/(lpr), MRL+/+ and C57BL/6 mice by real-time PCR and immunofluorescence. Adhesion molecule expression levels were compared to kidney pathology and adhesion molecule expression in the kidney. We found a significant upregulation of ICAM-1 and E-selectin mRNA in the kidneys from 14week-old MRL/(lpr) mice, which correlated with proteinuria and profound kidney damage. Moreover, despite the absence of marked brain histopathological changes, both ICAM-1 and E-selectin were also upregulated in brain tissue from these animals. There was a strong correlation of adhesion molecule expression levels in the kidney and the brain. Immunofluorescence studies revealed that ICAM-1 and E-selectin upregulation localizes to blood vessel walls, astrocytes related to the blood-brain barrier, and microglial cells. Our data indicate that cellular adhesion molecules in the brain are upregulated without evidence of overt brain damage, and that a strong relation exists with the levels of kidney damage. Therefore, brain involvement, even subclinical, should be presumed when peripheral organs are inflamed.
Department of Neuropathology, Otto-von-Guericke-University, Magdeburg, Germany.
Sebastian
S
Stielke
Gerburg
G
Keilhoff
Elmar
E
Kirches
Peter R
PR
Mertens
Klaus-Hinrich
KH
Neumann
George C
GC
Tsokos
Christian
C
Mawrin
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
D015815:Cell Adhesion Molecules