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Depletion and Reconstitution of Macrophages in Mice
08:50

Depletion and Reconstitution of Macrophages in Mice

Published on: August 1, 2012

Inactivation of lysosomal proteases by oxidized low density lipoprotein is partially responsible for its poor

G Hoppe1, J O'Neil, H F Hoff

  • 1Department of Cell Biology, Cleveland Clinic Foundation, Ohio 44195.

The Journal of Clinical Investigation
|October 1, 1994
PubMed

Insights

Oxidized LDL (ox-LDL) directly inactivates macrophage lysosomal proteases, specifically cathepsin B. This protease inactivation explains the deficient degradation of lipoproteins by macrophages, impacting lipid metabolism.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Lipid Metabolism

Background:

  • Deficient processing of apolipoprotein B in oxidized LDL (ox-LDL) by macrophage lysosomal proteases is known.
  • This deficiency has been attributed to modifications in apo B.

Purpose of the Study:

  • To investigate if direct inactivation of lysosomal proteases by ox-LDL contributes to deficient lipoprotein degradation.
  • To determine the specific protease involved in this ox-LDL-induced inhibition.

Main Methods:

  • Mouse peritoneal macrophages (MPM) were preincubated with ox-LDL, LDL, or aggregated LDL.
  • Lipoprotein degradation and uptake were measured using 125I-labeled lipoproteins.
  • Lysosomal thiol protease activity and cathepsin B activity in cell extracts were assessed.

Main Results:

  • Ox-LDL, but not LDL or aggregated LDL, inhibited subsequent lipoprotein degradation.
  • Lipoprotein uptake was unaffected, indicating inhibition at the degradation level.
  • MPM preincubated with ox-LDL showed reduced thiol protease activity and cathepsin B activity.

Conclusions:

  • Oxidized LDL directly inactivates macrophage lysosomal proteases, particularly cathepsin B.
  • This inactivation mechanism contributes to the impaired degradation of lipoproteins by macrophages.

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