Expression of inducible-NOS in human glomerulonephritis: the possible source is infiltrating monocytes/macrophages

Nitric oxide (NO) is a biological mediator which is synthesized from L-arginine by a family of nitric oxide synthases (NOS). In this paper, we have studied the expression of the inducible NO synthase (iNOS) in the tissues of the human kidney at the mRNA level by RT-PCR assay and at the protein level by an immunohistochemistry technique using a specific anti-macrophage NOS monoclonal antibody. Biopsied renal tissues from patients with IgA nephropathy (IgAN; 28 cases) and with non-IgA mesangial proliferative glomerulonephritis (PGN;12 cases), and normal renal tissues obtained from kidneys removed for malignancies (11 cases) were included in this experiment. iNOS message was present in about 73% tissues from IgAN and PGN patients, which was supported by histochemical findings and the iNOS positive cells were predominantly in the tubulointerstitial areas where infiltration of monocytes/macrophages was abundant. The iNOS positive tissues were also strongly positive for CD14, INF-gamma and TNF-alpha mRNA expression. In our in vitro study, iNOS expression was found only in cytokines (INF-gamma and TNF-alpha) stimulated monocytes/macrophages but not in lymphocytes and neutrophils. Normal renal tissues did not show any iNOS expression either at the mRNA level or at the protein level in this study. Clinical and histological data showed that decreased renal function and tubulointerstitial damage were greater in the iNOS expressing patients. This study demonstrates that there is some in vivo induction for iNOS expression, likely to be mediated by cytokines, for local NO production that might be involved in the initiation and/or progression of mesangial proliferative glomerulonephritis.