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fMLP Receptor Stimulated Activation of Macrophage: Its Effect on Killing of Intracellular Leishmania donovani

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Bioscience Reports

Abstract

The fMLP receptor of peritoneal macrophages stimulated by fMLP graftedliposomes as ligand, was analysed and compared with respective controlsfor its ability to promote killing of intracellular Leishmaniaparasites. fMLP grafted liposomes show greater efficacy in killingintracellular L. donovani (MHOM/IN/1983/AG83) parasites in a timedependent manner than free fMLP. fMLP grafted liposomes also releasemore active oxygen intermediates and reactive nitrogen intermediates(O− 2, H2O2, NO) than free fMLP. The key enzymes PKCand PTK for the respiratory burst and nitric oxide generation werefound to be important in this fMLP receptor mediated signaling processas the enzyme specific inhibitors viz. staurosporine, genistein andAG126 suppressed the leishmanicidal effect of fMLP graftedliposomes. The above findings suggest that the fMLP receptorof macrophages activates PKC and PTK mediated signalling thatis responsible for the intracellular parasite killing.

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REFERENCES

  1. Synderman, R. and Fudman, E. J. (1980) Demonstration of a chemotactic peptide receptor on macrophage. J. Immunol. 124:2754–2757.

    PubMed  Google Scholar 

  2. Niedel, J., Nillikinson, S., and Cuatrecasas (1979) Receptor mediated uptake and degradation of I125 chemotactic peptide by neutrophills. J. Biol. Chem. 264:10700–10706.

    Google Scholar 

  3. Baggiolini, M. and Kerran, K. P. (1992) Neutrophill activation control of shape changes exocytosis and the respiratory burst. New Physiol. Sci. 7:215–217.

    Google Scholar 

  4. Baggiolini, M., Bouley, F., Bandway, J. A., and Cournutte, J. T. (1993) Activation of neutrophil leukocytes: chemoattractant receptor and respiratory burst. FASEB. J. 7:1004–10010.

    PubMed  Google Scholar 

  5. Kikuchi, A., Kozawa, O., Kaibuchi, K., Kotada, T., Ui, M., and Takai, Y. (1986). Direct evidence for involvement of a guanine-nucleotide binding protein in chemotactic peptide stimulated formation of inositol biphosphate and triphosphate in differentiating human leukemic (HL60) cells. J. Biol. Chem. 261:11558–11562.

    PubMed  Google Scholar 

  6. Horn, W. and Karnovsky, M. L. (1986) Features of the translocation of Protein Kinase C in neutrophills stimulated with the chemotactic peptide f-MetLeu-Phe. Biochem. Biophys. Res. Commun. 139:1169–1175.

    PubMed  Google Scholar 

  7. Banerjee, G., Bhaduri, A. N., and Basu, M. K. (1994) Mannose coated liposomal hemocin in the treatment of experimental leishmaniasis in hamster. Biochem. Med. Metab. Biol. 53:1–7.

    PubMed  Google Scholar 

  8. Banerjee, G., Medda, S., and Basu, M. K. (1998) A novel peptide grafted liposomal delivery system targeted to macrophages. Antimicrobiol. Agent and Chemo. 42:348–351.

    Google Scholar 

  9. Chakraborty, P., Bhaduri, A. N., and Das, P. K. (1990) Sugar receptor mediated drug delivery to macrophages in the therapy of experimental visceral leishmaniasis. Biochem. Biophys. Res. Commun. 166:404–410.

    PubMed  Google Scholar 

  10. Vouldoukis, I., et al., (1995) The killing of L. Major by human macrophage is mediated by NO induced after ligation of FCRCD23 surface antigen. Proc. Natl. Acad. Sci. USA 92:7804–7808.

    PubMed  Google Scholar 

  11. Dasgupta, D., Chakraborty, P., and Basu, M. K. (2000) Ligation of Fc Receptor of macrophages stimulate PKC and antileishmanial activity. Mol. Cell. Biochem. 209:1–8.

    PubMed  Google Scholar 

  12. Gregoriadis, G. and Ryman, B. E. (1972) Liposomal localization and β-fructofuranosidases-coating liposomes injected into rat. Biochem. J. 129:123–133.

    PubMed  Google Scholar 

  13. Rist, R. J. and Naftalin, R. J. (1993) Glucose and PMA stimulated oxygen consumption and superoxide production in rat peritoneal macrophages is inhibited by dexamethasone. Biochem. J. 291:509–514.

    PubMed  Google Scholar 

  14. Nathan, C. F. and Root, R. K. (1977) Hydrogen perioxide release from mouse peritoneal macrophages. J. Exp. Med. 146:1648–1662.

    PubMed  Google Scholar 

  15. Green, L. C., Wagner, D. A., Glogwski, J. S., Skipper, P. L., Wishnok, J. S., and Tannebaus, SR. (1982) Analysis of nitrate, nitrite and [5N] nitrite in biological fluids. Anal. Biochem. 126:131–134.

    Google Scholar 

  16. Kodama, J., Hazeki, K., Hazeki, O., Okada, T. and Michid, U. (1999) Enhancement of chemotactic peptide induced activation of phosphoinositide-3-kinase by granulocyte-macrophage colony stimulating factor and its relation to the cytokine mediated priming of neutrophill superoxide anion production. Biochem. J. 337:201–209.

    PubMed  Google Scholar 

  17. Schmidt, H. H., Seifert, R., and Bohme, E. (1989) FEBS Lett. 244:357–360.,

    PubMed  Google Scholar 

  18. Browning, D., Des, D. N., and Richard, D. Ye (1999). Activation of p38 nitrogen activated protein kinase by lipopolysaccharide in human neutrophills requires nitric oxide dependent cGMP accumulation. J. Biol. Chem. 274:537–542.

    PubMed  Google Scholar 

  19. Schnyder, B., Meunier, P. C., and Car, B. D. (1998) tiBiochem. J.} 331:489–495.

  20. Huang, Z. H., Charles, S. J. H., Rathjan, A. D., Poulous, A., Murray, A. W., and Ferrante, A. (1997) N-6 and n-3 polyunsaturated fatty acids stimulate translocation of protein kinase Cα, Aβ1, Aβ11 and εand enhance against induced NADPH oxidase in macrophages. Biochem. J. 325:553–557.

    PubMed  Google Scholar 

  21. Stephens, L., Jackson, T., and Hawkins, P. T. (1993) Synthesis of phosphatidylinosito-3,4,5-triphosphate in permeabilized neutrophills regulated by receptor and G-proteins. J. Biol. Chem. 268:17162–17166.

    PubMed  Google Scholar 

  22. Planznik, A. T. R., Prossnitz, D. R., Yoswikawa, A., Sarcka, A. E., Trynor, K., and Bokouh, G. M. (1996) A tyrosine kinase signalling pathway account for the majority of phosphotidyl inositol, 3,4,5triphosphate formation in chemoattractant stimulated human macrophages. J. Biol. Chem. 271:25204–25212.

    PubMed  Google Scholar 

  23. Zu, Y. L., Ai, Y Gilherist, A., Labadia, M. E., Shatati, R. I., and Huang, C. K. (1996) Activation of MAPK kinase activated protein kinase 2 in human neutrophills after phorbol ester or fMLP peptide stimulation. Blood 87:5287–5294.

    PubMed  Google Scholar 

  24. Bommakanti, R. K., Bokoch, G. M., Tolley, J. O., Schreiber, R. E., Siemsen, D. W., Klotz, K. N., and Jesaitis, A. J. (1992) Reconstitution of a physical complex between the N-formyl-chemotactic peptide receptor and G-protein: inhibition by perfussis toxin-catalyzed ADP-ribosylation. J. Biol. Chem. 267:7576.

    PubMed  Google Scholar 

  25. Gierschik, P. D., Sidiropoulous and Jakobs, K. H. (1989). Two distinct Gi-proteins mediate formyl peptide receptor signal transduction in human leukemia (HL60) cells. J. Biol. Chem. 264:21470.

    PubMed  Google Scholar 

  26. Vlahos, C. J., et al. (1995) Investigation of neutrophill signal transduction using a specific inhibitor of phosphatidyl inositol-3-kinase. J. Immunol. 154:2413.

    PubMed  Google Scholar 

  27. Wilson, E., Glcott, M. C., Bell, R. M., Merill, A. H., and Lambeth, J. D. (1986) Inhibition of the oxidative burst in human neutrophills by spingoid long chain basis: role of protein kinase C in activation of the burst. J. Biol. Chem. 261:12616.

    PubMed  Google Scholar 

  28. Niwa, Y., Ozaki, Y., Kanoti, T., Akamatsu, H., and Kurisaka, M. (1996) Role of cytokines, Tyrosine kinase and protein kinase C on production of superoxide and induction of scavanging enzymes in human leukocytes. Clin. Immunol. Immunopathol. 79:303–307.

    PubMed  Google Scholar 

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  1. Biomembrane Division, Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Calcutta, 700032. Fax

    Dalia Dasgupta, Prasanta Chakraborty & Mukul K. Basu

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  1. Dalia Dasgupta
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  2. Prasanta Chakraborty
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  3. Mukul K. Basu
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Dasgupta, D., Chakraborty, P. & Basu, M.K. fMLP Receptor Stimulated Activation of Macrophage: Its Effect on Killing of Intracellular Leishmania donovani. Biosci Rep 20, 345–354 (2000). https://doi.org/10.1023/A:1010325916675

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