Related Experiment Videos
Lead inhibits oxidative metabolism of macrophages exposed to macrophage-activating factor
Y Buchmüller-Rouiller1, A Ransijn, J Mauël
1Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Abstract:
The present experiments were designed to evaluate the effect of lead on the capacity of macrophages to respond to activating signals by increased respiratory-burst activity. When mouse peritoneal macrophages were exposed for 24 h to macrophage-activating factor (MAF) and/or bacterial lipopolysaccharide in the presence of lead acetate, a marked inhibition of their oxidative metabolism was observed. The hexosemonophosphate-shunt (HMPS) activity and the release of oxygen derivatives upon triggering by phorbol myristate acetate (PMA) were impaired. Treatment with the metal for 1 h led, however, to stimulation rather than inhibition of the PMA-triggered superoxide production, suggesting that the metal interfered with neither the triggering steps nor the activity of the NADPH oxidase. Moreover, the lead-induced inhibition of macrophage oxidative metabolism did not result from blockade of enzymes of the HMPS pathway. Glucose-6-phosphate dehydrogenase in macrophage extracts, as well as CO2 production from glucose, remained unaffected by the presence of lead, and extracts of lead-treated macrophages were as active as extracts from control cells in those two assays. Lead appeared to interfere with an early event in the MAF-induced activation process. In addition, lead decreased the uptake of 2-deoxyglucose by macrophages, suggesting that the metal might inhibit trans-membrane glucose-transport systems, a phenomenon that might explain in part the metabolic inhibition observed in lead-treated cells.
Insights
Lead exposure inhibits macrophage immune response by impairing oxidative metabolism. This study reveals lead acetate disrupts macrophage-activating factor (MAF) signaling and glucose uptake, crucial for immune cell function.
Area of Science:
- Immunology
- Toxicology
- Cell Biology
Background:
- Macrophages are critical immune cells involved in host defense.
- Respiratory burst activity is a key macrophage function for pathogen killing.
- Environmental toxins like lead can impact immune cell function.
Purpose of the Study:
- To investigate the impact of lead acetate on macrophage respiratory burst activity.
- To determine the specific mechanisms by which lead affects macrophage activation.
- To assess lead's effect on macrophage oxidative metabolism and glucose uptake.
Main Methods:
- Mouse peritoneal macrophages were treated with lead acetate, macrophage-activating factor (MAF), and/or lipopolysaccharide.
- Respiratory burst activity was measured by oxygen derivative release triggered by phorbol myristate acetate (PMA).
- Hexosemonophosphate-shunt (HMPS) activity, glucose-6-phosphate dehydrogenase activity, and 2-deoxyglucose uptake were assessed.
Main Results:
- Lead acetate significantly inhibited macrophage oxidative metabolism and HMPS activity.
- PMA-triggered superoxide production was impaired in lead-exposed macrophages.
- Lead did not affect glucose-6-phosphate dehydrogenase activity but decreased 2-deoxyglucose uptake, suggesting interference with glucose transport.
Conclusions:
- Lead acetate inhibits macrophage activation by interfering with early signaling events.
- Lead's disruption of trans-membrane glucose transport contributes to metabolic inhibition in macrophages.
- These findings highlight lead's immunotoxic effects on macrophage function.