Anti-glomerular basement membrane glomerulonephritis in the mouse: the role of macrophages

An immunohistochemical study was undertaken on fixed, paraffin-embedded mouse kidney in order to elucidate the role and significance of infiltrating macrophages in a mouse model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). Tissue was available representing the full gamut of histological features seen in this model. The mouse macrophage-specific antigen F4/80 was detected in tissue sections of glomerulonephritic kidney and the pattern and extent of staining was compared with normal mouse kidney. In glomerulonephritic kidney, an increase in the number of F4/80-positive cells was evident in close proximity to and surrounding Bowman's capsule of those glomeruli which were severely damaged, with extensive fibrin deposition and well developed cellular crescents. F4/80-positive cells did not feature in the glomerular tuft or in the region of the parietal epithelium of Bowman's capsule even when extensive cellular crescents were present. Breaks in Bowman's capsule were not demonstrated. We conclude that F4/80-positive macrophages are not a major constitutive cell type of developing crescents in this mouse model of anti-GBM GN but, by virtue of their peri-glomerular localization, may be involved in the destructive process, perhaps producing signalling molecules which contribute to the inflammatory reaction.