Experimental glomerulonephritis induced by a low dose of anti-thy-1 antibody

Abstract

Background: Thy-1.1 nephritis is a widely used model of proliferative glomerulonephritis. Lesions are characterized by diffuse mesangiolysis and prominent ballooning of capillary loops, followed by severe mesangial proliferation. However, such severe lesions are not common in human mesangial proliferative nephritis. We analyzed mild-to-moderate mesangial proliferative nephritis induced by a lower dose of anti-Thy-1.1 antibody. Methods" We administered a low intravenous dose (0.02 mg/mL) of antibody to Wistar rats, and the histologic changes were observed by light and electron microscopy and by various immunopathologic methods. The serum complement level and distribution of polymorphonuclear leukocytes were also examined. Results" Diffuse mesangial-cell lysis occurred at day 1, but mesangial-matrix lysis was mild, and ballooning of capillary loops was rare. Mesangia] cell proliferation appeared at day 2 and reached its maximum at day 5, but it was milder than that seen in the usual dose (0.2 mg/mL) model. The glomerulus was repaired to almost normal structure by day 14. Residual mesangial matrices and endothelial cells seemed to prevent ballooning by making bridges with capillary basement membranes. In the healing stage, this low-dose model demonstrated mild vascular remodeling without active angiogenesis, while the usual-dose model of Thy-1 nephritis showed prominent angiogenic activity to reconstruct capillary tufts. Conclusion:The low-dose model of Thy-1 nephritis, which does not require prominent angiogenesis, may be more useful in analyzing the mechanism of glomerulonephritis than the usually adopted Thy-1 nephritis model, which showed drastic glomerular destruction and prominent angiogenesis.

Targeted gene therapy for rat glomerulonephritis using HVJ‐immunoliposomes

“…This observation is consistent with a previous report by K. Muroga et al . They demonstrated that chronic nephritis can be induced by using a high‐dose antibody and that reduced volume of antibody failed to induce glomerulonephritis34. Also, the small dose of antibody used in this study did not lead to any inducement in apparent damage to glomeruli, as shown in Figure 2.…”

Role of Glomerular Endothelial Damage in Progressive Renal Disease

“…We studied an experimental model of mild-degree Thy-1 nephritis with a small dose of the antibody [35]. We administered a 1/10 dose of anti-thy 1.1 monoclonal anti-body(OX-7) to Wistar rats, comparing the results with ordinary experimental dosages.…”