Experimental focal glomerular lesions elicited by insoluble immune complexes. Ultrastructural and immunofluorescent studies.

Injection of small amounts of ferritin intravenously, into the aorta (above the renal arteries) or into the left renal artery of rabbits hyperimmunized against this protein, results in the formation of circulating, insoluble, antigen-antibody complexes. Some of these complexes localize focally in the renal glomerular capillaries, where they elicit severe lesions. The fate of the complexes and the evolution of the lesions have been followed by immunofluorescent and electron microscopic techniques. Within a few hours, the deposition of complexes in the glomeruli resulted in a massive accumulation of neutrophils platelets, and fibrin, sometimes leading to acute focal necroses of some loops. These lesions were quite similar to those developing in the small dermal vessels during the Arthus reaction. Most of the complexes were rapidly phagocytosed and degraded by neutrophils; swelling and proliferation of endothelial and mesangial cells usually followed the acute damage and contributed to the removal of remaining complexes, cell debris, and fibrin deposits. Later, focal areas of mesangial proliferation and sclerosis were observed, containing large amounts of basement membrane-like material and sometimes of collagen fibrils; synechiae and crescent formation were noted in certain places. These observations suggest that the glomerular localization of very large, poorly soluble or insoluble immune complexes may be responsible for the focal glomerular changes seen in association with subacute bacterial endocarditis, with anaphylactoid purpura, or for some of the most severe lesions developing during chronic immune complex diseases.