Leukocyte analysis using monoclonal antibodies in human glomerulonephritis

Abstract

The leukocyte subpopulations were analyzed within both the glomeruli and the interstitium in renal biopsies from 145 patients with various forms of glomerulonephritis. Cells were identified by monoclonal antibodies to leukocyte cell-surface antigens and immunoperoxidase labelling. Leukocytes, as defined by a monoclonal antibody to the leukocyte common antigen (PHM1), were present in normal, human renal tissue in both glomeruli (2.8 +/- 0.6 cells/glom. cross section) and interstitium (102 +/- 18 cells/mm2). Monocytes constituted the predominant infiltrating cell type in normal glomeruli (1.3 +/- 0.2) and T cells were rarely found (0.3: range 0 to 0.8), whereas both monocytes (34 +/- 10/mm2) and T lymphocytes (33 +/- 14/mm2) were found in the normal interstitium. In the non-proliferative forms of glomerulonephritis there was no significant increase in the number of glomerular inflammatory cells when compared with normal glomeruli. However, significantly increased numbers of T lymphocytes were seen in the interstitium of biopsies with minor non-specific changes (67 +/- 15/mm2), membranous nephropathy (134 +/- 30/mm2), focal glomerulosclerosis (207 +/- 53/mm2), and diabetic nephropathy (198 +/- 81/mm2). In the proliferative forms of glomerulonephritis only crescentic GN and post-infectious GN demonstrated significantly-increased glomerular monocytes and granulocytes. There was no significant increase in the number of glomerular T cells when compared with normal glomeruli. However, there was a significant increase in the number of interstitial T lymphocytes in all forms of proliferative glomerulonephritis when compared with the normal interstitial cell population.(ABSTRACT TRUNCATED AT 250 WORDS)

Intrarenal production of B-cell survival factors in human lupus nephritis

“…In the glomerular compartment, few T cells, even fewer B cells and no dendritic cells are typically present. 29,46,47 Thus, macrophages, which we and others 48 could identify in glomeruli with lupus nephritis, may have a prominent role. Chang et al 9 show in vitro that BLyS stimulation of TACI expressing monocytes led to the enhancement of their survival and their activation.…”

Mononuclear Cell-Infiltrate Inhibition by Blocking Macrophage-Derived Chemokine Results in Attenuation of Developing Crescentic Glomerulonephritis

“…Glomerular Mo/M are associated with glomerular hypercellularity, crescent formation, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. 4,5 The reduced glomerular Mo/M infiltrates imply a subsequent decrease in Mo/M -derived mediators such as cytokines, growth factors, nitric oxide, and reactive oxygen intermediates, that are involved in glomerular injury. 50,51 The inhibition of Mo/M infiltration appears to be an important measure in preventing the progression of acute glomerular injury to irreversible tissue damage.…”

Interferon-γ Augments Acute Macrophage-Mediated Renal Injury Via a Glucocorticoid-Sensitive Mechanism

“…Macrophage accumulation is a common feature in most types of human glomerulonephritis (1). These cells have been implicated in causing renal injury on the basis that their accumulation correlates with renal dysfunction (2), and the density of macrophage infiltration is predictive of disease progression in IgA nephropathy and lupus nephritis (3,4).…”