PHENOTYPIC ANALYSIS OF THE GLOMERULAR AND PERIGLOMERULAR MONONUCLEAR CELL INFILTRATES IN THE THY .1.1. MODEL OF GLOMERULONEPHRITIS

BACKGROUND: The phenotype of macrophages invading the mesangium and pe riglomerular region has not been described in experimental mesangial p roliferative glomerulonephritis, although it has implications for the mechanism of entry of these cells into these locations and their funct ion once there. We have, therefore, determined the phenotype of the pe riglomerular leukocytic infiltrate in the Thy 1.1 model of mesangial p roliferative glomerulonephritis and compared it with that of cells inv ading the mesangium. EXPERIMENTAL DESIGN: The Thy 1.1 model was induce d in Lewis rats, and sections were taken at 1 hour and at 1, 4, 9, 30, and 90 days postinduction. Immunohistochemistry was performed using m onoclonal antibodies against macrophage markers (ED-1, CD4, RT1-B, and ED-2), chains of the beta(2) integrins (CD18, CD11a, and CD11b), T an d B cell markers (CD8, T cell receptor, interleukin-2 receptor, and MR C OX33), and markers of mesangial cell proliferation (proliferating ce ll nuclear antigen, cu-smooth muscle actin). Sections were compared wi th those obtained from control animals. RESULTS: In untreated rats, a striking resident periglomerular macrophage population (phenotype ED-1 (-ve) ED-2(-ve) CD4(-ve) RT1-B-+ve CD18(+ve) CD11a(+ve) CD11b(+ve)) wa s found, confirming a previous report. From 24 hours postinduction, th is resident macrophage population was supplemented by a population who se predominant phenotype (ED-1(+ve) ED-2(-ve) CD4(+ve) RT1-B-+ve CD18( +ve) CD11a(+ve) CD11b(+ve)) was identical to that of macrophages infil trating the mesangium. Both infiltrates peaked at 4 days and returned to base-line levels by 1 to 3 months. There was no significant lymphoc yte infiltrate within the glomerulus and only a minimal periglomerular T cell infiltrate. CONCLUSIONS: These data show, first, that disease limited to the mesangium can lead directly to periglomerular macrophag e infiltration. Second, the presence of CR3 (i.e., CD11b and CD18) and LFA-1 (i.e., CD11a and CD18) on the macrophage infiltrate indicates t hat both ligands are important for cells to enter the mesangium and pe riglomerular areas. Third, the marked phenotypic and temporal similari ties between the mesangial and periglomerular macrophage infiltrates s uggests that a common factor(s) is involved in their pathogenesis. Fin ally, expression of RT1-B (Ia) but not ED-2 is reported to be typical of interstitial dendritic cells rather than tissue macrophages, sugges ting a unique function for the glomerular and periglomerular macrophag e infiltrate in this model.