Abstract
Peritoneal macrophages pretreated with different stimulants were analysed and compared with their respective controls for their ability to kill intracellular pathogenic L. donovani, (MHOM/IN/1983/AG83) an isolate from Indian subcontinent. Stimulation of macrophages by zymosan showed a higher microbicidal activity as compared to that by PMA. A correlation between microbicidal activity of the macrophages and the parameters related to respiratory burst activity such as liberation of 02 −, production of H202 and consumption of 02 was sought. All the parameters showed a decrease in case of infected macrophages in comparison to those of the non-infected ones. Thus, it is possible that the impairment of macrophage activation by intracellular Leishmania contributes to their survival in the toxic environment of the host.
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Abbreviations
- 02 :
-
superoxide anion
- H202 :
-
hydrogen peroxide
- PMA:
-
phorbol 12-myristate 13-acetate
- PHPA:
-
phydroxylphenylacetic acid
- Hepes:
-
N-2-hydroxyethyl piperazine-N-2-ethyl sulphonic acid
References
Alexander J, Vickerman K: Fusion of host cell secondary lysosomes with the parasitophorous vaculeses of Leishmanic mexicana infected macrophages. J Protozool 22: 502–508, 1975
Chang K -P, Dwyer DM: Multiplication of a human parasite (Leishmania donovani) in phagolysosomes of hamster macrophages Science 193: 678–679, 1976
Beaman L, Beaman BL: The role of oxygen and its derivatives in microbial pathogenesis and host defense. Ann Rev Microbiol 38: 27–48, 1984
Buchmuller Y, Mauel J: Studies on the mechanism of macrophage activation: possible involvement of oxygen metabolites in killing of Leishmania enriettii by activated mouse macrophages. J Reticuloendothel Soc 29: 181–192, 1981
Distefano JF, 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 70: 252–260, 1983
Locksley RM, Klebanoff SJ: Oxygen dependent microbicidal systems of phagocytes and host defense against intracellular protozoa. J Cell Biochem 22: 173–185, 1983
Murray HW: Macrophage activation: enhanced oxidative and antiprotozoal activity. Curr Top Immunobiol 13: 97–115, 1984
Murray HW, Cartelli DM: Killing of intracellular Leishmania donovani by human mononuclear phagocytes. Evidence for oxygendependent and independent leishmanicidal activity. J Clin Invest 72: 32–44, 1983
Murray HW, Cohn ZA: Macrophage oxygen dependent antimicrobial activity. I. Susceptibility of Toxoplasma gondii to oxygen intermediate. J Exp Med 150: 938–949, 1979
Murray HW, Juangbhanich CW, Nathan CF, Cohn ZA: Macrophage oxygen dependent antimicrobial activity. II. Role of oxygen intermediates. J Exp Med 150: 950–964, 1979
Nathan CF, Silverstein SC, Brukner LH, Cohn ZA: Extracellular cytolysis by activated macrophages and granulocytes II. Hydrogen peroxide as a mediator of cytotoxicity. J Exp Med 149: 100–113, 1979
Philippeaux MM, Mauel J: Extracellular cytolysis by activated macrophages: studies with macrophages on permeable membrane. Immunobiol 167: 301–317, 1984
Chang K-P, Chaudhuri G: Molecular determinants of Leishmania virulence. Ann Rev Microbiol 44: 499–529, 1990
Mukherjee S, Ghosh C, Basu MK: Leishmania donovani: Role of microviscosity of macrophage membrane in the process of parasite attachment and internalization. Exptl Parasitol 66: 18–26, 1988
Johnston RB Jr, Godzik CA, Cohn ZA: Increased superoxide anion production by immunologically activated and chemically elicited macrophages. J Exp Med 148: 115–127, 1978
Lowry OH, Rosebrough NJ, Farr AL, Landall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275, 1951
Wymann MP, Tscharner VV, Deranteau DA, Baggiolini M: Chemiluminescence detection of H202 produced by Human neutrophile during the respiratory burst. Anal Biochem 165: 371–378, 1987
Nathan CF, Root RK: Hydrogen peroxide release from mouse peritoneal macrophages. J Exp Med 146: 1648–1662, 1977
Badwey JA, Kannovsky ML: Active oxygen species and the functions of phagocytic leukocytes. Ann Rev Biochem 49: 695, 1980
Murray HW: Susceptibility of Leishmania to oxygen intermediates and killing by normal macrophages. J Exp Med 153: 1302–1315, 1981
Murray HW: Interaction of Leishmania with a macrophage cell line. Correlation between intracellular killing and the generation of oxygen intermediates. J Exp Med 153: 1690–1695, 1981
Murray HW: Cell mediated immune response in experimental visceral leishmaniasis II. O2 dependent killing of intracellular Leishmania donovani amastigotes. J Immunol 129: 351–357, 1982
Murray HW, Cohn ZA: Macrophage oxygen-dependent antimicrobial activity III. Enhanced oxidative metabolism as an expression of macrophage activation. J Exp Med 152: 1596–1609, 1980
Wilson CB, Tsai V, Remington JS: Failure to trigger the oxidative burst by normal macrophages. Possible mechanism for survival of intracellular pathogens. J Exp Med 151: 328–346, 1980
Locksley RM, Wilson CB, Klebanoff SJ: Role for endogenous and acquired peroxidase in the toxoplasmacidal activity of murine and human mononuclear phagocytes. J Clin Investigation 69: 1099–1111, 1982
Nathan CF, Nogueira N, Juang-bhanech C, Ellis J, Cohn ZA: Activation of macrophage in vivo and in vitro. Correlation between hydrogen peroxidase release and killing of Trypanozoma cruzi. J Exp Med 149:1056–1068, 1979
Haidaris CG, Bonventre PF: A role on oxygen dependent mechanism in killing of Leismania donovani tissue forms by activated macrophages. J Immunol 129: 850–855, 1982
Olivier M, Brownsey RW, Reiner NE: Defective stimulus-response coupling in human monocytes infected with Leishmania donovani is associated with altered activation and translocation of protein kinase C. Proc Natl Acad Sci 89: 7481–7485, 1992
Paswell J, Shor R, Keren G, Messer G, El-On J: Comparison of the effect of various stimuli on Leishmanicidal capacity of human monocytes in vitro. Clinical and Exp Immunol 56: 553–558, 1984
Pearson RD, Harcus JL, Symes PH, Romito R, Donowitz GR: Failure of the phagoeytic oxidative response to protect human monocytederived macrophages from infection by Leishmania donovani. J Immunol 129: 1282–1286, 1982
Buchmuller-Rouiller Y, Mauel J: Impairment of the oxidative metabolism of mouse peritoneal macrophages by intracellular Leishmania spp. Infect Immun 55: 587–593, 1987
Murray HW: Pretreatment with phorbol myristate acetate inhibits macrophage activity against intracellular protozoa. J Reticuloendothel Soc 31: 479–487, 1982
Baggiolini M, Wymann MP: Turning on the respiratory burst. Tibs 15: 69–72, 1990
Remaley AT, Glew RH, Kuhns DB, Basford RE, Waggoner AS, Gmst LA, Pope M: Leishmania donovani: Surface membrane acid phosphatase blocks neutrophil oxidative metabolite production. J Biol Chem 260: 880–886, 1985
Cillari E, Arcoleo F, Dieli M, D'Agostino R, Gromo G, Leoni F, Melano S: The macrophage-activating tetrapeptide tuftsin induces nitric oxide syntesis and stimulates murine macrophages to kill Leishmania parasites in vitro. Infect Immun 62: 2649–2652, 1994
Ding HA, Nathan CF, Stuehr DJ: Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages: comparison of activating cytokines and evidence for independent production. J Immunol 141: 2407–2412, 1988
James SL, Hibbs JB Jr: The role of nitrogen oxides as effector molecules of parasite killing. Parasitol Today 6: 303–305, 1990
Liew FY, Millot S, Parkinson C, Palmer RMJ, Moncada S: Macrophage killing of Leishmania parasites in vivo is mediated by nitric oxide from L-Arginine. J Immunol 144: 4794–4797, 1990
Lin JY, Chadee K: Macrophage cytotoxicity against Entamoeba histolytica trophozoites is mediated by nitric oxide from L-arginine. J Immunol 148: 3999–4005, 1992
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Chakraborty, R., Mukherjee, S. & Basu, M.K. Oxygen-dependent Leishmanicidal activity of stimulated macrophages. Mol Cell Biochem 154, 23–29 (1996). https://doi.org/10.1007/BF00248457
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DOI: https://doi.org/10.1007/BF00248457