1. Human polymorphonuclear leucocyte elastase and cathepsin G were incubated with preparations of isolated human glomerular basement membrane at neutral pH and 37 degrees C. 2. The ability of these enzymes to degrade glomerular basement membrane was followed by the release of hydroxyproline. Both proteinases released considerable amounts of hydroxyproline. 3. By using Sephadex G-100 it was shown that the solubilized basement membrane fragments appeared as a single peak and had a molecular weight of over 100 000. These proteins after reduction were analysed by sodium dodecyl sulphate-gel electrophoresis to examine their subunit pattern and determine their molecular size. 4. The released basement membrane proteins gave at least four precipitin lines with a rabbit anti-(glomerular basement membrane) antiserum. 5. These results support the concept that polymorphonuclear leucocyte neutral proteinases play an important role in the pathogenesis of glomerulonephritis. 6. At acid pH values cathepsin B also released hydroxyproline from human glomerular basement membrane but the lysosomal carboxyl proteinase, cathepsin D, had no action.

Clinical Science and Molecular Medicine (1978), 54,667-672 Summary 1. Lysosomal proteinase activity was assayed in human cadaver kidney, urine, granules from poly morphonuclear leucocytes of normal persons, and urine samples from 154 patients with renal disease.2. Granules from polymorphonuclear leuco cytes showed proteinase activity at acid and neutral pH, whereas cadaver kidney showed proteinase activity at acid pH only.3. The urine from 13 patients with glomerulo nephritis showed proteinase activity at both acid and neutral pH as well as increased amounts of antigenic glomerular basement membrane frag ments. The properties of the urinary proteinases suggested that they had originated in polymorpho nuclear leucocytes.4. Only the urine samples containing these proteinases were capable of degrading isolated human glomerular basement membrane in vitro.5. Clinical recovery, where it occurred, was ac companied by the disappearance of urinary proteinase activity, and reduction in glomerular basement membrane antigen excretion.

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