Progressive Glomerulonephritis with Increasing Proteinuria Induced by a Second Attack to the Mesangial Cell

We have previously reported that two consecutive injections of the anti-Thy 1.1 monoclonal antibody (mAb) 1-22-3 with an interval of two weeks causes irreversible mesangial alterations. However, the precise mechanism of the development of these alterations was not fully elucidated. In this study, we first investigated the prognosis of rats receiving the second intravenous injection of the mAb 1-22-3 at five weeks after the first injection when the amount of urinary protein excretion normalized. Two consecutive injections of mAb with an interval of five weeks also caused irreversible mesangial alterations with persistent proteinuria (155.8±148.7mg/day at six months). To analyze the mechanism of the development of these alteration, we then compared the acute phase alterations after the second injection (two injection group) with those after the first injection (single injection group). Although no difference in the staining intensity of bound mAb 1-22-3, rat C3 in glomeruli and serum CH50 levels at 30 min after the last anti-Thy 1.1 mAb injection was detected in either group, the number of neutrophils infiltrating into glomeruli 30 min after the first injection of anti-Thy 1.1 mAb was larger than that at 30 min after the second injection (8.7±3.5 vs. 2.2±0.8 / gcs, p=0.0039). Additionally, the numbers of ED3 positive cells and CD8 positive cells infiltrating into glomeruli were significantly larger at five days after the second injection (two injection group) than after the first injection (single injection group). The results show that polymorphonuclear leukocyte (PMN) does not contribute to the progression of chronic glomerular lesions and that activated macrophages (ED3 positive cells) and CD8 positive cells are involved in the development and the progression of chronic glomerular lesions.