Inactivation of lysosomal proteases by oxidized low density lipoprotein is partially responsible for its poor degradation by mouse peritoneal macrophages.

G Hoppe, J O'Neil, HF Hoff - The Journal of clinical …, 1994 - Am Soc Clin Investig
G Hoppe, J O'Neil, HF Hoff
The Journal of clinical investigation, 1994Am Soc Clin Investig
Deficient processing of apo B in oxidized LDL (ox-LDL) by macrophage lysosomal
proteases has been documented and attributed to modifications in apo B. We have
investigated whether direct inactivation of lysosomal proteases by ox-LDL could also be
responsible for this deficient degradation. When mouse peritoneal macrophages (MPM)
were preincubated for 21 h at 37 degrees C with ox-LDL, LDL, or vortex-aggregated LDL,
only ox-LDL inhibited the subsequent degradation of 125I-labeled forms of the above …
Deficient processing of apo B in oxidized LDL (ox-LDL) by macrophage lysosomal proteases has been documented and attributed to modifications in apo B. We have investigated whether direct inactivation of lysosomal proteases by ox-LDL could also be responsible for this deficient degradation. When mouse peritoneal macrophages (MPM) were preincubated for 21 h at 37 degrees C with ox-LDL, LDL, or vortex-aggregated LDL, only ox-LDL inhibited the subsequent degradation of 125I-labeled forms of the above lipoproteins. Uptake of labeled lipoproteins was not appreciably affected by preincubation with ox-LDL, suggesting that the inhibition was at the level of lysosomal degradation. Thiol protease activity of cell extracts at pH 4.0, was reduced in MPM preincubated with ox-LDL relative to cells preincubated with LDL or medium alone. Extracts from untreated MPM, or mixtures of cathepsin B and D, showed a reduced ability to degrade 125I-LDL at pH 4.5 and reduced cathepsin B activity, after incubation with ox-LDL relative to incubation with LDL. Thus, the reduced degradation of lipoproteins in MPM pretreated with ox-LDL could be due to direct inactivation of the lysosomal protease, cathepsin B.
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