Glomerular chemokine expression and the effect of steroid and cyclophosphamide pulse therapy in human crescentic glomerulonephritis.
OBJECTIVE
To study glomerular expression of C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha and beta (MIP-1alpha, MIP-1beta) and the effect of steroid and cyclophosphamide (CTX) intermittent intravenous pulse therapy on expression in patients with crescentic glomerulonephritis (CGN) to further investigate the underlying mechanism of the treatment.


METHODS
Twelve patients with initial biopsy-proven CGN(2), 6 with lupus nephritis (lupus-CGN, LN-CGN) and 6 with vasculitis, (vasculitis-CGN, V-CGN) were enrolled in this study. They underwent an initial biopsy before steroid and CTX intermittent intravenous pulse therapy and were biopsied again one to three months later. Expression of MCP-1, MIP-1alpha, MIP-1beta, and CD68 in glomeruli with cellular and fibrocellular crescents were examined by immunohistochemical analysis in serial sections of renal biopsies. The effect of the pulse therapy on histopathological changes was also observed.


RESULTS
Although steroid and CTX intermittent intravenous pulse therapy markedly reduced the degree of glomerular crescent formation both in LN-CGN and V-CGN, the effect of the therapy on glomerular chemokine expression was significantly different between LN-CGN and V-CGN. It was found that steroid and CTX intermittent intravenous pulse therapy reduced the expression of CD68, MCP-1, and MIP-1alpha, but had no effect on MIP-1beta in glomeruli with cellular crescents of patients with LN-CGN. In patients with V-CGN, the therapy also reduced the expression of CD68, but had no effect on MCP-1, MIP-1alpha, and MIP-1beta in glomeruli with cellular crescents. It was noted that the degree of glomerulosclerosis and tubular interstitial fibrosis increased more significantly at the second biopsy in V-CGN as compared to LN-CGN.


CONCLUSIONS
The efficacy of steroid and CTX intermittent intravenous pulse therapy in CGN might be affected by reduction of glomerular chemokine expression. The different changes in glomerular expression of MCP-1 and MIP-1alpha in patients with LN-CGN and V-CGN after pulse therapy may correlate to different responses to treatment and prognosis.
Chen
Shufen
S
Nanjing University School of Medicine and Research Institute of Nephrology, Jinling Hospital, China.
Liu
Zhihong
Z
Chen
Huiping
H
Zhou
Hong
H
Wang
Jianping
J
Li
Leishi
L
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001706:Biopsy; D018932:Chemokine CCL2 / Q000032:analysis; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000032:analysis*; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D000097382:CD68 Molecule
D000305:Adrenal Cortex Hormones; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D003520:Cyclophosphamide; D019402:Macrophage Inflammatory Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule