Granulocyte lysosomal factors and plasma elastase in uremia: A potential factor of catabolism

Abstract

In uremic intoxication proteolytic activity in plasma and striated muscle is enhanced. To get further insights into the underlying mechanisms the lysosomal factors of polymorphonuclear (PMN) leukocytes and the plasma elastase-α₁-proteinase inhibitor complex were investigated in patients with acute and chronic renal failure. Lysosomal activity was evaluated in peripheral blood smears by the lysis of erythrocytes and plasma (halo formation) around each neutrophil induced by 0.25 M NaCl borate buffer. In about half of the patients with chronic renal insufficiency on dietary treatment lysosomal activity of PMN leukocytes was reduced. The plasma concentration of elastase-α₁-proteinase inhibitor complex was normal in most subjects, but increased in three patients with the highest serum creatinine levels (>13 mg/dl). In the patients with acute renal failure (ARF) of various origin (postoperatively, septicemia, pancreatitis, or dye-induced) halo formation was either reduced or absent. The plasma elastase-α₁-proteinase inhibitor complex was increased in 5/6 of the patients by a factor of two to four. Also in the patients on regular hemodialysis treatment halo formation of PMN leukocytes was substantially reduced, whereas the plasma levels of elastase-α₁-proteinase inhibitor complex was slightly increased. The finding of reduced lysosomal activity of PMN neutrophils in uremia may be partly due to an enhanced release of neutral proteinases into the circulation as indicated by the elevated plasma levels of elastase-α₁-proteinase inhibitor complex in some patients. This release might be in part due to the effect of “uremic toxins”. In the patients on hemodialysis treatment the contact of the blood with the dialyzer (cuprophane) membrane might be an additional factor. Moreover, in the patients with acute renal failure the underlying disease (infection, shock, trauma) contributes to the release of proteinases. These disturbances may be harmful to the patient if the blood concentration or function of the most important proteinase inhibitors (α₁-proteinase inhibitor,α₂-macroglobulin) is reduced.