Lead inhibits oxidative metabolism of macrophages exposed to macrophage-activating factor.
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.
Buchmüller-Rouiller
Y
Y
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Ransijn
A
A
Mauël
J
J
D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D007854:Lead / Q000494:pharmacology*; D008222:Lymphokines; D008262:Macrophage Activation / Q000187:drug effects; D016215:Macrophage-Activating Factors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009942:Organometallic Compounds / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects*; D010427:Pentose Phosphate Pathway / Q000187:drug effects
D008222:Lymphokines; D016215:Macrophage-Activating Factors; D009942:Organometallic Compounds; D007854:Lead; D005947:Glucose; C008261:lead acetate