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Glomerular basement membrane injury by neutrophil and monocyte neutral proteinases
Abstract:
Human peripheral blood leucocytes known to be present in the glomeruli of patients with certain forms of clinical glomerulonephritis have been investigated for their proteinase content and their ability to degrade glomerular basement membrane (GBM). Polymorphonuclear leucocytes (PMN) and monocytes, but not lymphocytes, contain neutral proteinases which extensively degrade GBM at physiological pH. Inhibitor studies indicate that the enzymes responsible are serine-type proteinases. The relative susceptibilities of the GBM to proteolytic attack showed that the monocyte preparation was considerably more active than the PMN neutral proteinases. The monocyte preparation also showed the ability to degrade GBM at acid pH. Lymphocytes had no effect on GBM either at acid or neutral pH. The possibility that the lysosomal proteinase of monocytes and PMNs are implicated in the damage to the GBM in glomerulonephritis is suggested.
Insights
Human white blood cells, specifically polymorphonuclear leucocytes (PMN) and monocytes, contain proteinases that degrade the glomerular basement membrane (GBM). Monocytes showed greater GBM degradation activity than PMNs, suggesting their role in glomerulonephritis.
Area of Science:
- Nephrology
- Immunology
- Biochemistry
Background:
- Human peripheral blood leucocytes infiltrate glomeruli in certain glomerulonephritis cases.
- The role of these infiltrating cells in glomerular basement membrane (GBM) damage is not fully understood.
Purpose of the Study:
- To investigate the proteinase content of human peripheral blood leucocytes.
- To assess their capacity to degrade the glomerular basement membrane (GBM).
Main Methods:
- Incubation of human peripheral blood leucocytes (polymorphonuclear leucocytes, monocytes, lymphocytes) with GBM.
- Analysis of GBM degradation at physiological and acid pH.
- Enzyme inhibitor studies to identify proteinase types.
Main Results:
- Polymorphonuclear leucocytes (PMN) and monocytes, but not lymphocytes, possess neutral proteinases that degrade GBM at physiological pH.
- Serine-type proteinases are identified as responsible for GBM degradation.
- Monocyte preparations exhibited significantly higher GBM degradation activity compared to PMN preparations.
- Monocyte preparations also degraded GBM at acid pH, while lymphocytes showed no effect.
Conclusions:
- Lysosomal proteinases from monocytes and PMNs are implicated in GBM damage in glomerulonephritis.
- Monocytes appear to play a more significant role than PMNs in this process.