MACROPHAGE-INDUCED GLOMERULAR INJURY - CELL TRANSFER STUDIES IN PASSIVE AUTOLOGOUS ANTIGLOMERULAR BASEMENT-MEMBRANE ANTIBODY-INITIATED EXPERIMENTAL GLOMERULONEPHRITIS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 51  (2) , 172-180
Abstract
The current studies were designed to assess the ability of mononuclear inflammatory cells to mediate glomerulonephritis (GN) by studying the effects of replacement of mononuclear inflammatory cells in rabbits depleted of all circulating leukocytes and in which an antibody-initiated, macrophage-dependent model of glomerular injury was induced. GN was initiated by the injection of sheep antirabbit glomerular basement membrane antibody. A proliferative endocapillary GN regularly occurred in which macrophages were the predominant infiltrating cell (mean 48.4 .+-. 16.1 SD macrophages/glomerulus) and heavy proteinuria developed (590 .+-. 152 mg/24 h). This lesion was shown to be dependent on the presence of circulating leukocytes as prior treatment with nitrogen mustard producing panleukopenia completely prevented macrophage accumulation (0.4 .+-. 0.1 macrophages/glomerulus), abnormal proteinuria (5.1 .+-. 1.6 mg/24 h) and histologic evidence of injury. When peritoneal mononuclear inflammatory cells were given i.v. (108) to nitrogen mustard-treated rabbits that were given the GN-inducing antibodies, a proliferative GN developed with significant macrophage accumulation (14.2 .+-. 4.8 macrophages/glomerulus), and some rabbits became proteinuric (38.8 .+-. 15.3 mg/24 h). EM indicated that glomerular endothelial cells underwent swelling and separation from the basement membrane in relation to macrophage accumulation. Control nitrogen mustard-treated animals given 108 mononuclear inflammatory cells without the injection of disease-initiating antibodies did not have glomerular macrophage accumulation (0.8 .+-. 0.3 macrophages/glomerulus), abnormal proteinuria (6.1 .+-. 2.1 mg/24 h) or any histologic abnormality. Thus, macrophages can accumulate in glomeruli in direct response to the deposition of antibody and produce a proliferative GN by both their own accumulation and their effects on intrinsic glomerular endothelial cells.