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Decrease of three lysosomal enzymes in guinea pig macrophages activated by lymphocyte mediators
1Departments of Medicine and Biological Chemistry, Harvard Medical School and Robert B. Brigham Hospital, Boston, Massachusetts.
Abstract:
Guinea pig peritoneal macrophages incubated for 72 h with MIF-rich medium which results in an activation of certain physiological functions have decreased specific activity of the lysosomal enzymes, acid phosphatase,Β-glucuronidase, and cathepsin D, and decreased phagocytosis of denatured particulate hemoglobin in comparison to control cells. Enhanced release of enzymes does not account for the decrease in lysosomal enzyme activity because these enzymes cannot be detected in the supernatant of the cells. Furthermore, when macrophages are activated by whole sensitized and stimulated lymphocytes, the specific activities of the lysosomal enzymes are also decreased or unchanged. It is therefore unlikely that the defense mechanisms of macrophages which are enhanced by lymphocyte mediators include an increase in lysosomal enzyme activity.
Insights
Activated guinea pig macrophages showed reduced lysosomal enzyme activity and phagocytosis. Lymphocyte activation also did not increase these macrophage defense mechanisms, challenging prior assumptions.
Area of Science:
- Immunology
- Cell Biology
Background:
- Macrophage activation is crucial for immune responses.
- Lysosomal enzymes and phagocytosis are key macrophage functions.
Purpose of the Study:
- To investigate the effect of macrophage-activating factors (MAFs) on lysosomal enzyme activity and phagocytosis in guinea pig macrophages.
- To determine if lymphocyte-derived mediators enhance macrophage defense mechanisms.
Main Methods:
- Guinea pig peritoneal macrophages were incubated with MIF-rich medium for 72 hours.
- Lysosomal enzyme activity (acid phosphatase, β-glucuronidase, cathepsin D) and phagocytosis of denatured hemoglobin were measured.
- Macrophages were also activated by sensitized and stimulated lymphocytes.
Main Results:
- Incubation with MIF-rich medium led to decreased specific activity of lysosomal enzymes and reduced phagocytosis.
- Enhanced enzyme release into the supernatant did not explain the decreased intracellular activity.
- Activation by lymphocytes resulted in unchanged or decreased lysosomal enzyme activity.
Conclusions:
- Macrophage activation by MIF-rich medium or lymphocyte mediators does not enhance lysosomal enzyme activity.
- Decreased lysosomal enzyme activity and phagocytosis suggest a complex regulatory mechanism during macrophage activation.
- The findings challenge the notion that increased lysosomal enzyme activity is a primary component of lymphocyte-mediated macrophage defense.
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