Biomedical subjects

S Tunesi

Publications and source records attributed to S Tunesi.

3 recordsLinked to original sources

PubMed1998

Transforming growth factor-beta, endothelin-1, and c-fos expression in necrotizing/crescentic IgA glomerulonephritis.

BACKGROUND: Among our cases of IgA glomerulonephritis (IgAGN), 10% show necrotizing/extracapillary lesions involving a small percentage of glomeruli and associated with a certain degree of inflammation in absence of glomerular and interstitial scarring. In our experience, also in repeat biopsies, these cases of IgAGN have a worse prognosis probably because necrotizing/extracapillary lesions can repeat and accumulate, leading to the progression of damage. As it is well known that transforming growth factor-beta (TGF-beta) and endothelin-1 (ET-1) are key-factors in the progression of glomerulonephritis, aim of the study was to examine their expression in renal biopsies of primary IgAGN with necrotizing/crescentic lesions in complete absence of interstitial fibrosis. To obtain information about the mitogenic effect of ET-1, the expression of c-fos, whose upregulation by ET-1 has been established in culture, was also studied. METHODS: Eighteen renal biopsies of patients with necrotizing/crescentic IgAGN were examined by immunohistochemistry with antibodies against TGF-beta, ET-1 and c-fos. The results were compared with those obtained on 22 cases of IgAGN characterized only by pure mesangial proliferation and 25 IgAGN biopsies with advanced, not active, glomerulointerstitial lesions. RESULTS: In necrotizing/crescentic IgAGN glomerular TGF-beta appeared more positive than in cases characterized only by pure mesangial proliferation and was especially expressed on cellular crescents. In the interstitium, TGF-beta, ET-1 and c-fos were expressed by infiltrating leukocytes, tubules, and small vessels. This positivity, although similar as localization, was less diffuse than in biopsies with advanced interstitial damage, but significantly greater than in cases with pure mesangial proliferation. CONCLUSIONS: Positivity of TGF-beta on cellular crescents is similar to that observed from other authors in different types of necrotizing/crescentic human glomerulonephritis and supports our hypothesis that this is a peculiar type of IgAGN. Moreover, interstitial expression of TGF-beta, ET-1 and c-fos in biopsies with glomerular active lesions but complete absence of interstitial fibrosis may potentially represent a signal of activation of mechanisms that induce and amplify the damage leading to further progression of the disease.

Adolescent↗

PubMed1996

Intraglomerular and interstitial leukocyte infiltration, adhesion molecules, and interleukin-1 alpha expression in 15 cases of antineutrophil cytoplasmic autoantibody-associated renal vasculitis.

In renal biopsy specimens from 15 patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated renal vasculitis, the infiltrating intraglomerular and interstitial leukocytes were localized and the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the cytokine interleukin-1 alpha (IL-1 alpha) were studied by an immunohistochemical method. Intraglomerular leukocytes were mainly macrophages (13.46 +/- 9.29 cells/glomerular cross-section) and, to a lesser extent, T lymphocytes (4.61 +/- 2.81 cells/glomerular cross-section). Staining with VCAM-1, which was negative in the undamaged tufts, was strongly positive in necrotizing-extracapillary lesions. Staining with ICAM-1 was also present in the damaged tufts, but its pattern was more diffuse. Intraglomerular IL-1 alpha was found in all biopsy specimens. Where the Bowman's capsule was not damaged, the periglomerular infiltrating cells were macrophages (42.6 +/- 25.2 cells/glomerular cross-section) and T lymphocytes (51.06 +/- 33.0 cells/glomerular cross-section). When there was a granulomatous lesion involving the glomerulus, the number of cells per granulomatous area revealed a massive number of CD45-positive leukocytes (345.83 +/- 237.47 cells/granulomatous lesion), many of them positive for activity markers (HLA-DR, IL-2R), adhesion molecules, and IL-1 alpha. Many activated cells were also present in interstitial areas of perivascular clusters of leukocytes, in which T lymphocytes (prevalently CD4+ cells) outnumbered the macrophages (331.55 +/- 207.85 cells/0.05 mm2 area v 125.68 +/- 60.57 cells/0.05 mm2 area). Adhesion molecules and IL-1 alpha were found in both tubular and vascular areas in all biopsy specimens. Our data strongly support the involvement of both the adhesion molecules ICAM-1 and VCAM-1 in the recruitment of intraglomerular leukocytes in renal vasculitis, indicate that VCAM-1 is a very good marker of necrotizing-extracapillary damage, and suggest its crucial connection with the macrophage recruitment in these vasculitic lesions. The presence of histochemically detectable levels of IL-1 alpha in glomeruli, tubules, and vessels and on some inflammatory cells supports its involvement in the vasculitic lesions, probably by triggering a positive feedback that increases the damage.

Adult↗

PubMed1996

Adhesion molecules expression in noncrescentic acute post-streptococcal glomerulonephritis.

Clinicomorphological features of 11 cases of non-crescentic acute post-streptococcal glomerulonephritis (APSGN) were reviewed. Intraglomerular and interstitial leukocytes and their possible correlation with the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-leukocyte adhesion molecule-1 (ELAM-1/E-selectin) were investigated by an immunohistochemical method. Intraglomerular leukocytes were primarily granulocytes (11.4 +/- 10 cells/glomerular cross-section) and monocytes-macrophages (13.4 +/- 19.4 cells/glomerular cross-section). The granulocytes outnumbered monocytes-macrophages in 7 of 11 specimens. The number of intraglomerular leukocytes correlated with proteinuria at the time of renal biopsy. Intraglomerular ICAM-1 staining was strongly positive in all biopsies, especially when intraglomerular monocytes-macrophages prevailed. Expression of intraglomerular VCAM-1 and E-selectin in diseased kidneys did not differ from that in normal kidneys. Interstitial leukocytes were primarily monocytes-macrophages (158.9 +/- 96.8 cells/mm2) and T lymphocytes (102.2 +/- 63.9 cells/mm2). The number of interstitial leukocytes, especially monocytes-macrophages, correlated with serum creatinine level at the time of biopsy. Interstitial ICAM-1 staining was strongly positive on tubules, peritubular capillaries, and small vessels. The tubular positivity for ICAM-1 correlated with the number of interstitial monocytes-macrophages. Interstitial VCAM-1 and E-selectin were expressed as in normal kidney tissues. The data from this study demonstrate that APSGN is characterized by the presence of both intraglomerular and interstitial leukocyte infiltration, correlating respectively with proteinuria and serum creatinine at the time of renal biopsy. Among the adhesion molecules studied, ICAM-1 seems the most involved in leukocyte recruitment, especially in that of monocytes-macrophages.

Acute Disease↗