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Association between leukocyte infiltration and development of glomerulosclerosis in experimental lupus nephritis
Author(s) -
Kootstra Carine J.,
Sutmuller Marjolein,
Baelde Hans J.,
de Heer Emile,
Bruijn Jan Anthonie
Publication year - 1998
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199802)184:2<219::aid-path990>3.0.co;2-9
Subject(s) - lupus nephritis , infiltration (hvac) , immunology , glomerulosclerosis , medicine , nephritis , pathology , proteinuria , kidney , disease , physics , thermodynamics
Mice with chronic graft‐versus‐host disease (GvHD) induced by injection of DBA/2 lymphocytes into (DBA/2×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×BL10 (BALB/c GvHD) and BALB.D2 into BALB.D2×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. © 1998 John Wiley & Sons, Ltd.