Induction of systemic lupus erythematosus syndrome in BALB/c mice by immunization with active chromatin.
OBJECTIVE
To establish an animal model for systemic lupus erythematosus (SLE)-like syndrome in mice.


METHODS
BALB/c mice were immunized with active chromatin isolated from ConA-activated syngeneic spleno-lymphocytes. Plasma samples of mice were tested by enzyme-linked immunosorbent assays (ELISA) for the presence of IgG anti-dsDNA, -ssDNA, and anti-histone antibodies. Tumor necrosis factor-alpha (TNF-alpha) in serum was measured by ELISA. Spleno-lymphocyte proliferation assays and the levels of interferon-gamma (IFN-gamma) in supernatants were tested respectively. Proteinuria was measured. Kidneys were examined by direct immunohistochemical method and light microscopy.


RESULTS
Anti-ds DNA, ssDNA, and histone antibodies were induced in active chromatin-immunized mice, the proliferation response of splenocytes to ConA and LPS were reduced, levels of interferon-gamma in supernatants and TNF-alpha in serum were lowered. Lupus nephritis was assessed by the presence of Ig deposits, glomerular pathology and proteinuria.


CONCLUSIONS
The active chromatin-induced SLE-like mouse model was similar to idiopathic SLE in human.
Li
Hong
H
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 200032, China.
Zhang
Yun-Yi
YY
Sun
Ya-Nan
YN
Huang
Xi-Yi
XY
Jia
Yong-Feng
YF
Li
Duan
D
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D002455:Cell Division; D002843:Chromatin; D004247:DNA / Q000276:immunology; D004277:DNA, Single-Stranded / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006657:Histones / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis; D007371:Interferon-gamma / Q000097:blood; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000139:chemically induced / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001323:Autoantibodies; D002843:Chromatin; D004277:DNA, Single-Stranded; D006657:Histones; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D004247:DNA