Association between leukocyte infiltration and development of glomerulosclerosis in experimental lupus nephritis.
Mice with chronic graft-versus-host disease (GvHD) induced by injection of DBA/2 lymphocytes into (DBA/2 x C57BL/10) F1 hybrids (DBA/2 GvHD) develop a lupus-like glomerulonephritis with global glomerulosclerosis 12 weeks after induction of the disease. In two other strain combinations with similar H-2 incompatibilities [BALB/c into BALB/c x BL10 (BALB/c GvHD) and BALB.D2 into BALB.D2 x BL10 (BALB.D2 GvHD)], GvHD induction leads to lupus nephritis without global glomerulosclerosis. This study investigated the identity of kidney-infiltrating leukocytes and their involvement in the development of glomerulosclerosis in these three strain combinations. In mice with DBA/2 GvHD, a significant increase in glomerular CD11a-positive cells was found 4 weeks after disease induction. Mice with BALB/c or BALB.D2 GvHD did not show an increase in glomerular CD11a-positive cells at any time point. In the interstitium, CD11a-positive cells were observed 4 weeks after disease induction only in mice with DBA/2 GvHD. In mice with BALB.D2 GvHD, no increase was found in interstitial CD11a-positive cells. In mice with BALB/c GvHD, interstitial CD11a-positive cells were found from week 4 onward. Further immunohistochemical analysis of the glomerular CD11a-positive cells in mice with DBA/2 GvHD showed that these cells were neither polymorphonuclear leukocytes (PMN), nor CD3-positive (T cells), B220-positive (B cells), or F4/80-positive (macrophages). They were all CD45-positive (leukocytes) and MHC class II-positive. In conclusion, we have shown in this model of chronic lupus nephritis that glomerular influx of as yet unidentified CD11a-positive leukocytes is associated with the development of glomerulosclerosis.
Kootstra
C J
CJ
Department of Pathology, Leiden University Hospital, The Netherlands.
Sutmuller
M
M
Baelde
H J
HJ
de Heer
E
E
Bruijn
J A
JA
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology; D006086:Graft vs Host Disease / Q000276:immunology*; D007105:Immune Complex Diseases / Q000276:immunology / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology; D007962:Leukocytes / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
D016169:Lymphocyte Function-Associated Antigen-1