Apoptosis of glomerular cells is an early manifestation of immunecomplex-mediated glomerulonephritis in the rat

Immunecomplex-mediated diseases result in cell injury that ranges from mild membrane perturbation to apoptosis and cellular necrosis. Anti-Thy1 antibody when injected into rats induces glomerular cell injury followed by cell proliferation. Apoptosis has been detected at late stages of the disease by in situ nick-end labeling (TUNEL) technique. We investigated the expression of proteins known to regulate apoptosis by immunohistochemistry in rats with anti-Thy1 nephritis. Rats develop mesangiolysis within 24 hours after injection, modest cellular repopulation at day 3 with prominent hypercellularity at day 7 which subsides by day 14 and day 28. Within 90 minutes after the injection of anti-Thy1 antibody, approximately 10% of glomerular cells showed apoptosis by TUNEL technique. Glomerular expression of proapoptotic proteins interleukin converting enzyme (ICE), Cpp32 and Bax was increased. The expression of Bcl-2, a protein that protects against apoptosis was also increased. Double immunohistochemical staining utilizing ED1 as a monocyte/macrophage marker indicated that the expression of these proteins is predominantly by intrinsic glomerular cells. Very few (<2%) apoptotic cells were observed at days 7, 14, and 28. These data indicate a biphasic role of apoptosis in glomerular injury. An early phase that contributes to cell injury and hypocellularity and a late phase that contributes to resolution of proliferative glomerulonephritis.