Monitoring urinary levels of monocyte chemotactic and activating factor reflects disease activity of lupus nephritis

Abstract

Monocytes/macrophages (M phi) have been implicated in the pathogenesis of lupus nephritis (LN), but the precise molecular mechanism of recruitment and activation of M phi in LN remains unclear. To clarify the involvement of chemotactic cytokines (chemokines) in those events, we measured levels of monocyte chemotactic and activating factor (MCAF, also termed monocyte chemoattractant protein-1, MCP-1) in urines and sera derived from 42 patients with LN. Both urinary and serum MCAF levels were significantly higher in patients with LN as compared with 22 healthy volunteers (10.3 +/- 3.2 vs. 1.0 +/- 0.1 pg/ml . creatinine, 212.2 +/- 75.8 vs. 66.1 +/- 15.5 pg/ml, respectively, P < 0.05, mean +/- SEM). Histological examination of renal lesions from 41 patients classified 19 as active according to the WHO-defined classes IIIb, IVb and IVc, and 22 as inactive by the WHO-defined classes I, II, IIIc, IVd and V. Urinary MCAF levels in the patients with active lesions were significantly higher than those with inactive lesions (20.3 +/- 6.4 vs. 1.7 +/- 0.3 pg/ml . creatinine, P < 0.01). Moreover, elevated urinary MCAF levels were dramatically decreased during steroid therapy-induced convalescence in 29 patients examined serially (13.9 +/- 4.5 vs. 5.3 +/- 1.7 pg/ml . creatinine, P < 0.001), whereas serum MCAF levels did not change significantly. Endothelial cells, renal epithelial cells and infiltrating mononuclear cells in the tubulointerstitial regions were MCAF-positive in immunohistochemical as well as in situ hybridization analysis. These observations suggest that MCAF is probably involved in the pathogenesis of LN with active lesions, possibly through the recruitment and activation of M phi, and that measurement of urinary MCAF levels may be a useful clinical tool for monitoring the disease activity of LN.

MCP-1 Induces Inflammatory Activation of Human Tubular Epithelial Cells

“…Thus TECs, in addition to mesangial cells and infiltrating mononuclear cells (25), might contribute to the increased urinary excretion of MCP-1. Urinary MCP-1 levels reflect the disease activity of lupus nephritis (26) and correlate with the extent of proteinuria and the number of glomerular macrophages in various glomerular diseases in humans (27). Glomerular expression of MCP-1 has been documented in experimental and human glomerulopathies (28,29).…”

Chemokines in renal diseases

“…reduced the renal expression of chemokines and their cognate receptors in accordance with the decrease in the clinical activities of human renal diseases (19)(20)(21)(22)(23)(24)(25).…”

“…Secondly, urinary MCP-1 levels were significantly higher in patients with advanced renal diseases, and were correlated with pathological progressive factors such as mesangial proliferation, crescentic formation and interstitial lesions associated with CD68 positive Mφ in patients with IgA nephropathy, lupus nephritis, crescentic glomerulonephritis and other inflammatory renal diseases (20,(22)(23).…”

“…and in situ hybridization analyses (20,(22)(23). Collectively, these observations suggest (Table 1).…”

DNA-dependent Activator of Interferon-regulatory Factors (DAI) Promotes Lupus Nephritis by Activating the Calcium Pathway

“…As in human lupus, kidney disease, especially lupus nephritis, is a major cause of morbidity, which is generally thought to be triggered by deposition of autoantibodies and the subsequent leukocyte infiltration and inflammation (15,16). Emerging data reveal that renal infiltrating macrophages (M) are prominent * This work was supported by grants of National Natural Science Foundation within the inflamed kidneys, which contributes to tissue damage in lupus nephritis by mediating many processes associated with inflammation, proteinuria, complement activation, and excessive tissue remodeling (17)(18)(19)(20). Recently, accumulating data demonstrate that renal macrophage infiltration is associated with poor disease outcome in SLE disease (21,22).…”