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. 1984 Nov;20(5):837–842. doi: 10.1128/jcm.20.5.837-842.1984

Oxygen metabolism in phagocytes of leprotic patients: enhanced endogenous superoxide dismutase activity and hydroxyl radical generation by clofazimine.

Y Niwa, T Sakane, Y Miyachi, M Ozaki
PMCID: PMC271453  PMID: 6096396

Abstract

We examined the generation of active oxygens (O2-, H2O2, and OH X ) and the superoxide dismutase (SOD) activity of polymorphonuclear leukocytes (PMNs) and monocytes from 14 leprotic patients manifesting a bacillary index above 2.2. Patients with disease of more than 4 years in duration showed significantly enhanced SOD activity and a decrease in O2- and OH X production. The antileprotic agent, clofazimine, significantly increased the generation of OH X in a dose-dependent manner, with a subsequent decrease in H2O2, but had no effect on the SOD activity of the PMNs and monocytes. In medium containing FeSO4 or Fe2+-EDTA, the drug elevated OH X production markedly further. Phagocytic SOD in PMNs and monocytes of leprotic patients was both host and bacillus derived, because the presence of cyanide, to which human-derived cuprozinc SOD is susceptible, did not completely abrogate SOD activity. The difficulty in treating leprosy may be partly ascribable to decreased phagocytic OH X generation, which in leprosy patients is apparently due to the uptake of Hansen bacillus-derived SOD. Clofazimine may be effective in leprosy by chelating Fe2+, with the resultant potentiation of the catalyzing activity of Fe2+ in the Haber-Weiss reaction increasing OH X formation from H2O2.

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Selected References

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  1. Ambruso D. R., Johnston R. B., Jr Lactoferrin enhances hydroxyl radical production by human neutrophils, neutrophil particulate fractions, and an enzymatic generating system. J Clin Invest. 1981 Feb;67(2):352–360. doi: 10.1172/JCI110042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbieri T. A., Correa W. M. Human macrophage culture. The leprosy prognostic test (LPT). Int J Lepr Other Mycobact Dis. 1967 Jul-Sep;35(3):377–381. [PubMed] [Google Scholar]
  3. Bullock W. E., Jr, Ho M. F., Chen M. J. Quantitative and qualitative studies of the local cellular exudative response in leprosy. J Reticuloendothel Soc. 1974 Nov;16(5):259–268. [PubMed] [Google Scholar]
  4. COCHIN J., AXELROD J. Biochemical and pharmacological changes in the rat following chronic administration of morphine nalorphine and normorphine. J Pharmacol Exp Ther. 1959 Feb;125(2):105–110. [PubMed] [Google Scholar]
  5. Crapo J. D., McCord J. M., Fridovich I. Preparation and assay of superoxide dismutases. Methods Enzymol. 1978;53:382–393. doi: 10.1016/s0076-6879(78)53044-9. [DOI] [PubMed] [Google Scholar]
  6. Fridovich I. Quantitative aspects of the production of superoxide anion radical by milk xanthine oxidase. J Biol Chem. 1970 Aug 25;245(16):4053–4057. [PubMed] [Google Scholar]
  7. Garcia-Gonzalex J. E., Rojas-Espinosa O., Estrada-Parra S. Phagocytosis in leprosy. I. The levels of "diaphorase", beta-glucuronidase, acid phosphatase, alkaline phosphatase and lipase in circulating leucocytes. Lepr Rev. 1977 Mar;48(1):17–26. doi: 10.5935/0305-7518.19770004. [DOI] [PubMed] [Google Scholar]
  8. Ichihara K., Kusunose E., Kusunose M., Mori T. Superoxide dismutase from Mycobacterium lepraemurium. J Biochem. 1977 May;81(5):1427–1433. [PubMed] [Google Scholar]
  9. Kark E. C., Davis B. R., Pomeranz J. R. Pyoderma gangrenosum treated with clofazimine. Report of three cases. J Am Acad Dermatol. 1981 Feb;4(2):152–159. doi: 10.1016/s0190-9622(81)70018-5. [DOI] [PubMed] [Google Scholar]
  10. Kusunose M., Noda Y., Ichihara K., Kusunose E. Superoxide dismutase from Mycobacterium species, strain Takeo. Arch Microbiol. 1976 May 3;108(1):65–73. doi: 10.1007/BF00425094. [DOI] [PubMed] [Google Scholar]
  11. Lindgren S., Enerbäck L., Freiberg N. Oral acantholytic itching disease responding to dapsone. Dermatitis herpetiformis, pemphigus, or a new disease? Oral Surg Oral Med Oral Pathol. 1976 Nov;42(5):597–605. doi: 10.1016/0030-4220(76)90211-5. [DOI] [PubMed] [Google Scholar]
  12. Mandell G. L., Hook E. W. Leukocyte bactericidal activity in chronic granulomatous disease: correlation of bacterial hydrogen peroxide production and susceptibility to intracellular killing. J Bacteriol. 1969 Oct;100(1):531–532. doi: 10.1128/jb.100.1.531-532.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McCord J. M. Free radicals and inflammation: protection of synovial fluid by superoxide dismutase. Science. 1974 Aug 9;185(4150):529–531. doi: 10.1126/science.185.4150.529. [DOI] [PubMed] [Google Scholar]
  14. McCord J. M., Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969 Nov 25;244(22):6049–6055. [PubMed] [Google Scholar]
  15. McDougall A. C., Horsfall W. R., Hede J. E., Chaplin A. J. Splenic infarction and tissue accumulation of crystals associated with the use of clofazimine (Lamprene; B663) in the treatment of pyoderma gangrenosum. Br J Dermatol. 1980 Feb;102(2):227–230. doi: 10.1111/j.1365-2133.1980.tb05697.x. [DOI] [PubMed] [Google Scholar]
  16. Michaëlsson G., Molin L., Ohmann S., Gip L., Lindström B., Skogh M., Trolin I. Clofazimine. A new agent for the treatment of pyoderma gangrenosum. Arch Dermatol. 1976 Mar;112(3):344–349. [PubMed] [Google Scholar]
  17. Molin L. Clofazimine-enhanced phagocytosis in pustulosis palmaris et plantaris. Acta Derm Venereol. 1975;55(2):151–153. [PubMed] [Google Scholar]
  18. NASH T. The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem J. 1953 Oct;55(3):416–421. doi: 10.1042/bj0550416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Niwa Y., Miyake S., Sakane T., Shingu M., Yokoyama M. Auto-oxidative damage in Behçet's disease--endothelial cell damage following the elevated oxygen radicals generated by stimulated neutrophils. Clin Exp Immunol. 1982 Jul;49(1):247–255. [PMC free article] [PubMed] [Google Scholar]
  20. Niwa Y., Sakane T., Miyachi Y. Dissociation of the inhibitory effect of dapsone on the generation of oxygen intermediates--in comparison with that of colchicine and various scavengers. Biochem Pharmacol. 1984 Aug 1;33(15):2355–2360. doi: 10.1016/0006-2952(84)90705-6. [DOI] [PubMed] [Google Scholar]
  21. Niwa Y., Sakane T., Shingu M., Yokoyama M. M. Effect of stimulated neutrophils from the synovial fluid of patients with rheumatoid arthritis on lymphocytes--a possible role of increased oxygen radicals generated by the neutrophils. J Clin Immunol. 1983 Jul;3(3):228–240. doi: 10.1007/BF00915347. [DOI] [PubMed] [Google Scholar]
  22. Rojas-Espinosa O. Phagocytosis in leprosy. 2. Production of superoxide by circulating blood leukocytes from lepromatous patients. Int J Lepr Other Mycobact Dis. 1978 Jul-Dec;46(3-4):337–341. [PubMed] [Google Scholar]
  23. Rosen H., Klebanoff S. J. Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte. J Exp Med. 1979 Jan 1;149(1):27–39. doi: 10.1084/jem.149.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rosen H., Klebanoff S. J. Role of iron and ethylenediaminetetraacetic acid in the bactericidal activity of a superoxide anion-generating system. Arch Biochem Biophys. 1981 May;208(2):512–519. doi: 10.1016/0003-9861(81)90539-7. [DOI] [PubMed] [Google Scholar]
  25. Salin M. L., McCord J. M. Free radicals and inflammation. Protection of phagocytosine leukocytes by superoxide dismutase. J Clin Invest. 1975 Nov;56(5):1319–1323. doi: 10.1172/JCI108208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sher R., Anderson R., Glover A., Wadee A. A. Polymorphonuclear cell function in the various polar types of leprosy and erythema nodosum leprosum. Infect Immun. 1978 Sep;21(3):959–965. doi: 10.1128/iai.21.3.959-965.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stach J. L., Fumoux F., Strobel M., Baret A., Michelson M. Augmentation de l'activité dismutasique dans les leucocytes spléniques de souris sensibles au BCG et à Mycobacterium lepraemurium. C R Seances Acad Sci III. 1981 Nov 16;293(10):575–578. [PubMed] [Google Scholar]
  28. Stendahl O., Molin L., Dahlgren C. The inhibition of polymorphonuclear leukocyte cytotoxicity by dapsone. A possible mechanism in the treatment of dermatitis herpetiformis. J Clin Invest. 1978 Jul;62(1):214–220. doi: 10.1172/JCI109109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Swanbeck G., Wennersten G. Effect of beta-carotene on photohemolysis. Acta Derm Venereol. 1973;53(4):283–289. [PubMed] [Google Scholar]
  30. Takigawa M., Miyachi Y., Uehara M., Tagami H. Treatment of pustulosis palmaris et plantaris with oral doses of colchicine. Arch Dermatol. 1982 Jul;118(7):458–460. [PubMed] [Google Scholar]
  31. WINKELMANN R. K., DITTO W. B. CUTANEOUS AND VISCERAL SYNDROMES OF NECROTIZING OR "ALLERGIC" ANGIITIS: A STUDY OF 38 CASES. Medicine (Baltimore) 1964 Jan;43:59–89. doi: 10.1097/00005792-196401000-00003. [DOI] [PubMed] [Google Scholar]
  32. WINKELMANN R. K., ROTH H. L. Dermatitis herpetiformis with acantholysis or pemphigus with response to sulfonamides: report of two cases. Arch Dermatol. 1960 Sep;82:385–390. doi: 10.1001/archderm.1960.01580030079010. [DOI] [PubMed] [Google Scholar]
  33. Ward P. A., Goralnick S., Bullock W. E. Defective leukotaxis in patients with lepromatous leprosy. J Lab Clin Med. 1976 Jun;87(6):1025–1032. [PubMed] [Google Scholar]
  34. Winston G. W., Cederbaum A. I. NADPH-dependent production of oxy radicals by purified components of the rat liver mixed function oxidase system. I. Oxidation of hydroxyl radical scavenging agents. J Biol Chem. 1983 Feb 10;258(3):1508–1513. [PubMed] [Google Scholar]

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