Cell Biology – Immunology – Pathology
Kidney International (1998) 54, 143–151; doi:10.1046/j.1523-1755.1998.00978.x
Local macrophage proliferation in human glomerulonephritis
Niansheng Yang, Nicole M Isbel, David J Nikolic-Paterson, Youji Li, Rengao Ye, Robert C Atkins and Hui Y Lan
Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia, and Department of Nephrology, First Affiliated Hospital of Sun Yat-Sen University of Medical Sciences, Guangzhou, People's Republic of China
Correspondence: Dr Hui Y. Lan, Department of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia. E-mail:huiLan@its-mmcc1.cc.monash.edu.au
Received 11 October 1997; Revised 11 February 1998; Accepted 11 February 1998.
Abstract
Local macrophage proliferation in human glomerulonephritis.
Background
Local macrophage proliferation has been described in several animal models of glomerulonephritis (GN), but its significance in human disease is unknown.
Methods
Double immunostaining for CD68 and the proliferating cell nuclear antigen (PCNA) was used to identify macrophage proliferation in 84 biopsies from a variety of glomerulonephridities.
Results
A small resident population of glomerular and interstitial CD68+ macrophages was identified in normal human kidney, of which only 1 to 2% showed evidence of proliferation on the basis of PCNA expression. A mild macrophage infiltrate, with only occasional proliferating macrophages, was seen in the less aggressive forms of GN (minimal change disease, non-IgA mesangioproliferative GN and IgA nephropathy). This was in sharp contrast to the more aggressive forms of disease (lupus class IV, vasculitis-associated GN, crescentic GN and mesangiocapillary proliferative GN), in which the prominent macrophage infiltrates contained many proliferating macrophages, accounting for 28 to 47% of the total macrophage population. Macrophage proliferation was largely restricted to areas of severe tissue damage (glomerular segmental proliferative lesions, crescents and foci of tubulointerstitial damage), suggesting that local proliferation is a mechanism for amplifying macrophage-mediated injury. Glomerular and interstitial macrophage proliferation gave a significant correlation with loss of renal function (P < 0.0001) and histologic lesions (P < 0.0001), but not with proteinuria. Interstitial T-cell proliferation also gave a significant correlation with loss of renal function and histologic damage, even though proliferation within the T-cell population was much lower than in the macrophage population.
Conclusions
This study demonstrates that macrophage proliferation is a feature of the more aggressive forms of human GN. Local proliferation may be an important mechanism for amplifying macrophage-mediated renal injury. In addition, the degree of local macrophage proliferation may be a useful diagnostic and prognostic indicator for human GN.
Keywords:
macrophage, proliferation, T cell, PCNA, Ki-67, glomerulonephritis, granulomatosus lesions, renal injury, crescents
Abbreviations:
APAAP, alkaline phosphatase anti-alkaline phosphatase complexes; cres GN, crescent glomerulonephritis; FCS, fetal calf serum; FGS, focal glomerulosclerosis; GBM, glomerular basement membrane; gcs, glomerular cross section; GM-CSF, granulocyte-macrophage colony-stimulating factor; GN, glomerulonephritis; IgAN, immunoglobulin A nephropathy; lupus II, lupus nephritis WHO class II; lupus IV, lupus nephritis WHO class IV; mAb, monoclonal antibodies; MCD, minimal change disease; MCPGN, mesangiocapillary proliferative glomerulonephritis; M-CSF, macrophage colony-stimulating factor; memb GN, membranous GN; MIF, macrophage migration inhibitory factor; non-IgA MPGN, non-IgA mesangial proliferative glomerulonephritis; PAP, peroxidase anti-peroxidase complexes; PBS, phosphate buffered saline; PCNA, proliferating cell nuclear antigen; vasc GN, nephritis associated with vasculitis
