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Background and objectives: Neuropilin-1 (NP-1), a functional vascular endothelial growth factor (VEGF) receptor, is important in the priming of resting T cells and contributes to the development of peripheral tolerance. Semaphorins, a family of axon guidance molecules, has been found to be involved in regulating the immune system.The aim of this study was to explore the involvement of NP-1 and semaphorins in lupus glomerulonephritis (LGN).Methods: Twelve kidney biopsies from LGN patients and five normal biopsies were examined in this study. In addition, eight biopsies from patients with primary nephropathy and proteinuria were included serving as a disease control group. Biopsies were stained with anti-VEGF, NP-1, and semaphorins. The Image Pro-Plus software was used to measure the intensity and extent of staining. The correlation with clinico-pathological parameters was evaluated.Results: VEGF expression was slightly higher in LGN. NP-1 and semaphorins were stained with significantly higher intensity in LGN when compared with both the normal and the disease control groups. NP-1 deposits were found only in damaged glomerulus areas and positively correlated with clinico-pathological parameters of renal disease (a statistical trend). However, the semaphorins were found in inverse correlations.Discussion: Being present in normal and slightly increased in diseased glomeruli, VEGF is considered protective during inflammation. Increased NP-1 expression in LGN may intensify the possible protective effect of VEGF, thereby preventing endothelial damage. However, one should consider the possibility that increased NP-1 expression is harmful and could play a role in the damage of LGN. NP-1 is suggested to be a reliable marker differentiating focal versus diffuse LGN. Semaphorin 3A can serve as a histological marker for tubular damage. The altered ability of kidneys to secrete semaphorins during advanced renal damage may in part explain its inverse correlation with renal function. Further work is needed in order to better understand the role of NP-1 and semaphorins in LGN. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase (MMP)-9 is produced by many inflammatory cells such as macrophages, neutrophils, mast cells, eosinophils and T lymphocytes. Activated T cells are capable, through cell–cell contact, of inducing MMP-9 expression in human mast cells.To investigate the activation status of peripheral CD4+ T cells and the level of MMP-9 in the plasma of patients with chronic urticaria (CU), and whether MMP-9 levels are in association with CU severity.Study subjects included 29 patients with CU and 30 healthy control subjects. At the time of assessment, patients were divided into subgroups according to urticarial severity. Plasma levels of total MMP-9 (free pro-MMP-9 and free MMP-9) were determined by ELISA. CD4+ lymphocytes were positively selected with magnetic microbeads. After 48 h of activation, CD4+ T cells were assayed for both nuclear factor-kappaB (NF-κB) expression and proliferation.Plasma levels of MMP-9 were found to be significantly higher in 29 CU patients compared with 18 healthy controls (186±174 vs. 31±21 ng/mL,P<0.0001). We also found a significant correlation between MMP-9 levels and urticarial severity (r=0.92,P<0.001). In addition, CD4+ T cells from CU patients expressed higher levels of NF-κB than CD4+ T cells from healthy controls (82±30 vs. 69±20 optical density,P=0.007). Finally, as compared with seven healthy individuals, DNA synthesis in CD4+ T cells from seven CU patients was found to be significantly elevated (1000±240 vs. 751±166 counts per minute,P=0.01).Increased levels of MMP-9 are found in CU patients, and particularly among those with severe disease. We also demonstrated that CD4+ T cells from such patients are highly activated. [ABSTRACT FROM AUTHOR]