Abstract
The mechanism by which macrophages kill facultative intracellular parasites is not known. A test system is described utilizing human macrophages derived from blood monocytes and the opportunistic pathogen Listeria monocytogenes. In this system, bacterial killing was impaired under hypoxic conditions. Under aerobic conditions, addition of Clofazimine (B663), a phenazine derivative effective in the treatment of human leprosy, potentiated the killing of Listeria by macrophages. Potentiation occurred at drug concentrations usually attainable in man and which are not directly injurious to the bacteria. The enhanced bactericidal activity occurred only in the presence of oxygen; the drug induced increased leukocyte oxygen consumption which was insensitive to cyanide.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baehner R. L., Karnovsky M. L. Deficiency of reduced nicotinamide-adenine dinucleotide oxidase in chronic granulomatous disease. Science. 1968 Dec 13;162(3859):1277–1279. doi: 10.1126/science.162.3859.1277. [DOI] [PubMed] [Google Scholar]
- Cline M. J. Bactericidal Activity of Human Macrophages: Analysis of Factors Influencing the Killing of Listeria monocytogenes. Infect Immun. 1970 Aug;2(2):156–161. doi: 10.1128/iai.2.2.156-161.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cline M. J., Swett V. C. The interaction of human monocytes and lymphocytes. J Exp Med. 1968 Dec 1;128(6):1309–1325. doi: 10.1084/jem.128.6.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohn Z. A. The structure and function of monocytes and macrophages. Adv Immunol. 1968;9:163–214. doi: 10.1016/s0065-2776(08)60443-5. [DOI] [PubMed] [Google Scholar]
- Holmes B., Page A. R., Good R. A. Studies of the metabolic activity of leukocytes from patients with a genetic abnormality of phagocytic function. J Clin Invest. 1967 Sep;46(9):1422–1432. doi: 10.1172/JCI105634. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klebanoff S. J. Myeloperoxidase-halide-hydrogen peroxide antibacterial system. J Bacteriol. 1968 Jun;95(6):2131–2138. doi: 10.1128/jb.95.6.2131-2138.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lehrer R. I., Cline M. J. Leukocyte myeloperoxidase deficiency and disseminated candidiasis: the role of myeloperoxidase in resistance to Candida infection. J Clin Invest. 1969 Aug;48(8):1478–1488. doi: 10.1172/JCI106114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paul B., Sbarra A. J. The role of the phagocyte in host-parasite interactions. 13. The direct quantitative estimation of H2O2 in phagocytizing cells. Biochim Biophys Acta. 1968 Feb 1;156(1):168–178. doi: 10.1016/0304-4165(68)90116-5. [DOI] [PubMed] [Google Scholar]
- Vischer W. A. Antimicrobial activity of the leprostatic drug 3-(p-chloranilino)-10(p-chlorphenyl)-2,10-dihydro-2-(isopropylimino)-phenazine (G 30 320). I. Studies in vitro. Arzneimittelforschung. 1968 Dec;18(12):1529–1535. [PubMed] [Google Scholar]
- Vischer W. A. The experimental properties of G 30 320 (B 663)--a new anti-leprotic agent. Lepr Rev. 1969 Apr;40(2):107–110. doi: 10.5935/0305-7518.19690021. [DOI] [PubMed] [Google Scholar]
- Zatti M., Rossi F., Patriarca P. The H2O2-production by polymorphonuclear leukocytes during phagocytosis. Experientia. 1968 Jul 15;24(7):669–670. doi: 10.1007/BF02138302. [DOI] [PubMed] [Google Scholar]
- Zeya H. I., Spitznagel J. K. Cationic protein-bearing granules of polymorphonuclear leukocytes: separation from enzyme-rich granules. Science. 1969 Mar 7;163(3871):1069–1071. doi: 10.1126/science.163.3871.1069. [DOI] [PubMed] [Google Scholar]