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. 1989 Jun 1;260(2):325–332. doi: 10.1042/bj2600325

Lead inhibits oxidative metabolism of macrophages exposed to macrophage-activating factor.

Y Buchmüller-Rouiller 1, A Ransijn 1, J Mauël 1
PMCID: PMC1138672  PMID: 2669732

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.

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Selected References

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  1. Baumgarten H. A simple microplate assay for the determination of cellular protein. J Immunol Methods. 1985 Sep 3;82(1):25–37. doi: 10.1016/0022-1759(85)90221-2. [DOI] [PubMed] [Google Scholar]
  2. Bonventre P. F., Mukkada A. J. Augmentation of glucose transport in macrophages after particle ingestion. Infect Immun. 1974 Dec;10(6):1391–1396. doi: 10.1128/iai.10.6.1391-1396.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buchmüller-Rouiller Y., Mauël J. Correlation between enhanced oxidative metabolism and leishmanicidal activity in activated macrophages from healer and nonhealer mouse strains. J Immunol. 1986 May 15;136(10):3884–3890. [PubMed] [Google Scholar]
  4. Buchmüller Y., Mauel J. Studies on the mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from concanavalin A-stimulated lymphocytes. J Exp Med. 1979 Aug 1;150(2):359–370. doi: 10.1084/jem.150.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buchmüller Y., Mauel J. Studies on the mechanisms of macrophage activation: possible involvement of oxygen metabolites in killing of Leishmania enrietti by activated mouse macrophages. J Reticuloendothel Soc. 1981 Mar;29(3):181–192. [PubMed] [Google Scholar]
  6. Castranova V., Bowman L., Miles P. R., Reasor M. J. Toxicity of metal ions to alveolar macrophages. Am J Ind Med. 1980;1(3-4):349–357. doi: 10.1002/ajim.4700010311. [DOI] [PubMed] [Google Scholar]
  7. De la Harpe J., Nathan C. F. A semi-automated micro-assay for H2O2 release by human blood monocytes and mouse peritoneal macrophages. J Immunol Methods. 1985 Apr 22;78(2):323–336. doi: 10.1016/0022-1759(85)90089-4. [DOI] [PubMed] [Google Scholar]
  8. DiStefano J. F., Beck G., Zucker S. Mechanism of BCG-activated macrophage-induced tumor cell cytotoxicity: evidence for both oxygen-dependent and independent mechanisms. Int Arch Allergy Appl Immunol. 1983 Mar;70(3):252–260. doi: 10.1159/000233332. [DOI] [PubMed] [Google Scholar]
  9. Granick J. L., Sassa S., Kappas A. Some biochemical and clinical aspects of lead intoxication. Adv Clin Chem. 1978;20:287–339. doi: 10.1016/s0065-2423(08)60025-6. [DOI] [PubMed] [Google Scholar]
  10. Hilbertz U., Krämer U., De Ruiter N., Baginski B. Effects of cadmium and lead on oxidative metabolism and phagocytosis by mouse peritoneal macrophages. Toxicology. 1986 Apr;39(1):47–57. doi: 10.1016/0300-483x(86)90158-7. [DOI] [PubMed] [Google Scholar]
  11. Howard J. K. Human erythrocyte glutathione reductase and glucose 6-phosphate dehydrogenase activities in normal subjects and in persons exposed to lead. Clin Sci Mol Med. 1974 Nov;47(5):515–520. doi: 10.1042/cs0470515. [DOI] [PubMed] [Google Scholar]
  12. Karl L., Chvapil M., Zukoski C. F. Effect of zinc on the viability and phagocytic capacity of peritoneal macrophages. Proc Soc Exp Biol Med. 1973 Apr;142(4):1123–1127. doi: 10.3181/00379727-142-37190. [DOI] [PubMed] [Google Scholar]
  13. Kelso A., Glasebrook A. L., Kanagawa O., Brunner K. T. Production of macrophage-activating factor by T lymphocyte clones and correlation with other lymphokine activities. J Immunol. 1982 Aug;129(2):550–556. [PubMed] [Google Scholar]
  14. Kiremidjian-Schumacher L., Stotzky G., Dickstein R. A., Schwartz J. Influence of cadmium, lead, and zinc on the ability of guinea pig macrophages to interact with macrophage migration inhibitory factor. Environ Res. 1981 Feb;24(1):106–116. doi: 10.1016/0013-9351(81)90137-7. [DOI] [PubMed] [Google Scholar]
  15. Kiyotaki C., Peisach J., Bloom B. R. Oxygen metabolism in cloned macrophage cell lines: glucose dependence of superoxide production, metabolic and spectral analysis. J Immunol. 1984 Feb;132(2):857–866. [PubMed] [Google Scholar]
  16. Kowolenko M., Tracy L., Mudzinski S., Lawrence D. A. Effect of lead on macrophage function. J Leukoc Biol. 1988 Apr;43(4):357–364. doi: 10.1002/jlb.43.4.357. [DOI] [PubMed] [Google Scholar]
  17. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  18. Lachant N. A., Tomoda A., Tanaka K. R. Inhibition of the pentose phosphate shunt by lead: a potential mechanism for hemolysis in lead poisoning. Blood. 1984 Mar;63(3):518–524. [PubMed] [Google Scholar]
  19. Loose L. D., Silkworth J. B., Simpson D. W. Influence of cadmium on the phagocytic and microbicidal activity of murine peritoneal macrophages, pulmonary alveolar macrophages, and polymorphonuclear neutrophils. Infect Immun. 1978 Nov;22(2):378–381. doi: 10.1128/iai.22.2.378-381.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. MacGowan A. P., Peterson P. K., Keane W., Quie P. G. Human peritoneal macrophage phagocytic, killing, and chemiluminescent responses to opsonized Listeria monocytogenes. Infect Immun. 1983 Apr;40(1):440–443. doi: 10.1128/iai.40.1.440-443.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mauel J., Buchmüller Y., Behin R. Studies on the mechanisms of macrophage activation. I. Destruction of intracellular Leishmania enriettii in macrophages activated by cocultivation with stimulated lymphocytes. J Exp Med. 1978 Aug 1;148(2):393–407. doi: 10.1084/jem.148.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mauel J., Schnyder J., Baggiolini M. Intracellular parasite killing induced by electron carriers. II. Correlation between parasite killing and the induction of oxidative events in macrophages. Mol Biochem Parasitol. 1984 Sep;13(1):97–110. doi: 10.1016/0166-6851(84)90104-x. [DOI] [PubMed] [Google Scholar]
  23. Murray H. W. Cell-mediated immune response in experimental visceral leishmaniasis. II. Oxygen-dependent killing of intracellular Leishmania donovani amastigotes. J Immunol. 1982 Jul;129(1):351–357. [PubMed] [Google Scholar]
  24. Murray H. W. Susceptibility of Leishmania to oxygen intermediates and killing by normal macrophages. J Exp Med. 1981 May 1;153(5):1302–1315. doi: 10.1084/jem.153.5.1302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nathan C. F., Silverstein S. C., Brukner L. H., Cohn Z. A. Extracellular cytolysis by activated macrophages and granulocytes. II. Hydrogen peroxide as a mediator of cytotoxicity. J Exp Med. 1979 Jan 1;149(1):100–113. doi: 10.1084/jem.149.1.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nelson D. J., Kiremidjian-Schumacher L., Stotzky G. Effects of cadmium, lead, and zinc on macrophage-mediated cytotoxicity toward tumor cells. Environ Res. 1982 Jun;28(1):154–163. doi: 10.1016/0013-9351(82)90164-5. [DOI] [PubMed] [Google Scholar]
  27. Philippeaux M. M., Mauel J. Extracellular cytolysis by activated macrophages: studies with macrophages on permeable membranes. Immunobiology. 1984 Oct;167(4):301–317. doi: 10.1016/S0171-2985(84)80002-9. [DOI] [PubMed] [Google Scholar]
  28. Pick E., Charon J., Mizel D. A rapid densitometric microassay for nitroblue tetrazolium reduction and application of the microassay to macrophages. J Reticuloendothel Soc. 1981 Dec;30(6):581–593. [PubMed] [Google Scholar]
  29. Pick E., Mizel D. Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J Immunol Methods. 1981;46(2):211–226. doi: 10.1016/0022-1759(81)90138-1. [DOI] [PubMed] [Google Scholar]
  30. Seow W. K., Smith S. E., McCormack J. G., Thong Y. H. Uptake of 3H-deoxyglucose as a microassay of human neutrophil and monocyte activation. J Immunol Methods. 1987 Apr 2;98(1):113–118. doi: 10.1016/0022-1759(87)90443-1. [DOI] [PubMed] [Google Scholar]
  31. Vallee B. L., Ulmer D. D. Biochemical effects of mercury, cadmium, and lead. Annu Rev Biochem. 1972;41(10):91–128. doi: 10.1146/annurev.bi.41.070172.000515. [DOI] [PubMed] [Google Scholar]
  32. WICK A. N., DRURY D. R., NAKADA H. I., WOLFE J. B. Localization of the primary metabolic block produced by 2-deoxyglucose. J Biol Chem. 1957 Feb;224(2):963–969. [PubMed] [Google Scholar]

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