Not the ED1^+ but the ED3^+ Macrophage Participates in the Pathogenesis of Irreversible Glomerular Changes

We compared the acute phase responses of mesangial cells and inflammatory cells in reversible and irreversible mesangial alterations. We used a reversible model that induced by a single injection of anti-Thy 1.1 monoclonal antibody (mAb) 1-22-3,and an irreversible model of glomerulonephritis induced by two consecutive injections of mAb 1-22-3 with an interval of 2 weeks. Similar mesangiolysis occurred in both models. However, pathological phenotypic changes in the mesangial cell began more rapidly and markedly after the second wave of mesangiolysis. Glomerular mRNA expression of platelet-derived growth factor (PDGF) was higher in the irreversible model than in the reversible model, whereas mRNA expression of monocyte chemoattractant protein-1 (MCP-1) was lower in the irreversible model. The numbers of polymorphonuclear cell (PMN) and ED1^+ monocytes/macrophages were lower in the irreversible model than in the reversible model. By contrast, the recruitment of ED3^+ cells into the glomeruli was dominant in the irreversible model. A dual labeling study showed that major parts of ED3^+ cells in the glomeruli of the irreversible model were ED1 negative. ED3^+ ED1^- cells were not detected at any time in the reversible model. The ED3^+ cell should be regarded as an important candidate for acting on the mesangial cell to lead to irreversible mesangial alterations.