van Leer E H, de Roo G M, Bruijn J A, Hoedemaeker P J, de Heer E
Department of Pathology, University of Leiden, The Netherlands.
Exp Nephrol. 1993 Sep-Oct;1(5):292-300.
Passive Heymann nephritis (PHN) in the rat is induced by the administration of heterologous antibodies to renal tubular epithelium (RTE). The nephritogenic capacity of anti-RTE resides primarily in the antibody fraction directed against a 330-kD glycoprotein (gp330). However, monospecific anti-gp330 antibodies are less nephritogenic than anti-RTE antibodies. This discrepancy led us to study a possible synergizing role for different antibody specificities present within anti-RTE. The enzyme dipeptidyl peptidase type IV (DPP IV) is, like gp330, present in RTE as well as in the glomerulus. Anti-DPP IV antibodies have been shown to induce an acute, transient proteinuria. In this study, we investigated the nephritogenic effect of separate or simultaneous administration of heterologous anti-DPP IV and anti-gp330 antibodies. Injection of anti-DPP IV antibodies resulted in a short-lived glomerular binding, and in a dose-dependent polyuria, albuminuria or proteinuria. Binding of anti-gp330 antibodies was slower, but much more stable. Albuminuria could only be observed in the heterologous phase. Combined injection did not alter antibody-binding kinetics of either antibody nor the albuminuria induced by anti-gp330. However, in the presence of anti-gp330 antibodies, a lower dose of anti-DPP IV was capable to induce transient albuminuria as compared to anti-DPP IV alone. In conclusion, anti-DPP IV and anti-gp330 antibodies bind to different sites in the glomerulus with different kinetics. The presence of anti-gp330 deposits facilitated anti-DPP-IV-induced renal injury.
大鼠被动型海曼肾炎（PHN）是通过给肾小管上皮（RTE）注射异种抗体诱导产生的。抗RTE的致肾炎能力主要存在于针对330-kD糖蛋白（gp330）的抗体组分中。然而，单特异性抗gp330抗体的致肾炎性比抗RTE抗体弱。这种差异促使我们研究抗RTE中存在的不同抗体特异性可能的协同作用。二肽基肽酶IV型（DPP IV）酶与gp330一样，存在于RTE以及肾小球中。抗DPP IV抗体已被证明可诱导急性、短暂性蛋白尿。在本研究中，我们调查了单独或同时注射异种抗DPP IV和抗gp330抗体的致肾炎作用。注射抗DPP IV抗体导致短暂的肾小球结合，并引起剂量依赖性多尿、白蛋白尿或蛋白尿。抗gp330抗体的结合较慢，但更稳定得多。白蛋白尿仅在异种期观察到。联合注射既不改变任何一种抗体的抗体结合动力学，也不改变抗gp330诱导的白蛋白尿。然而，与单独使用抗DPP IV相比，在存在抗gp330抗体的情况下，较低剂量的抗DPP IV能够诱导短暂性白蛋白尿。总之，抗DPP IV和抗gp330抗体以不同的动力学结合到肾小球中的不同位点。抗gp330沉积物的存在促进了抗DPP-IV诱导的肾损伤。
