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The priming effect of halogenated phospholipids on the functional responses of human neutrophils

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Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Halogenated lipids formed in the reactions with myeloperoxidase (MPO)-derived species may contribute to the regulation of the functional activity of cells. In the present study we have investigated the effects of chloro- and bromohydrins formed in the HOCl and HOBr reactions, respectively, with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) on three different functional responses of human neutrophils: H2O2 generation, degranulation (MPO exocytosis), and cell aggregation. It was shown that POPC chloro- and bromohydrins (POPC-Cl and POPC-Br) induced the priming of neutrophils, resulting in significant upregulation of cell responses to neutrophil stimulators such as N-formyl-Met-Leu-Phe and lectin from Solanum tuberosum. The stimulating effects of POPC-Cl and POPC-Br were observed at low micromolar concentrations (liposomal concentration of POPC, 0.5–5 μM; the content of POPC-Cl or POPC-Br, 38 ± 3% of total lipids) after a short exposure (about 5 min) of the neutrophils to POPC-Cl or POPC-Br. These results suggest that halogenated lipids formed in vivo via MPO-dependent reactions may be considered as a new class of biologically active substances that are potentially able to contribute to the priming of myeloid cells in the sites of inflammation and serve as inflammatory response modulators.

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Abbreviations

ROS:

reactive oxygen species

LDL:

low-density lipoproteins

HOCl-LDL:

HOCl-modified LDL

MPO:

myeloperoxidase

fMLF:

N-formyl-Met-Leu-Phe

GlcNAc:

N-acetyl-D-glucosamine

MALDI-TOF:

(matrix assisted laser desorption/ionisation time-of-flight), mass spectrometry

POPC:

1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine

LS-POPC:

liposomes formed of POPC

POPC-Cl:

POPC chlorohydrins

POPC-Br:

POPC bromohydrins

STA:

lectin of potato tubers (Solanum tuberosum)

References

  1. Dale D.C., Boxer L., Liles W.C. 2008. The phagocytes: neutrophils and monocytes. Blood. 112, 935–945.

    Article  CAS  PubMed  Google Scholar 

  2. Klebanoff S. J. 2005. Myeloperoxidase: Friend and foe. J. Leukoc. Biol. 77, 598–625.

    Article  CAS  PubMed  Google Scholar 

  3. Baldus S., Heeschen C., Meinertz T., Zeiher A.M., Eiserich J.P., Münzel T., Simoons M.L., Hamm C.W. 2003. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation. 108, 1440–1445.

    Article  CAS  PubMed  Google Scholar 

  4. Klebanoff S.J. 1968. Myeloperoxidase-halide-hydrogen peroxide antibacterial system. J. Bacteriol. 95, 2131–2138.

    CAS  PubMed  Google Scholar 

  5. Zemskov V.M. 1984. Phagocytosis: Physiological and molecular aspects. Uspekhi sovremennoy biologii (Rus.). 98, 219–233.

    CAS  Google Scholar 

  6. Midwinter R.G., Vissers M.C., Winterbourn C.C. 2001. Hypochlorous acid stimulation of the mitogen-activated protein kinase pathway enhances cell survival. Arch. Biochem. Biophys. 394, 13–20.

    Article  CAS  PubMed  Google Scholar 

  7. Vile G.F., Rothwell L.A., Kettle A.J. 1998. Hypochlorous acid activates the tumor suppressor protein p53 in cultured human skin fibroblasts. Arch. Biochem. Biophys. 359, 51–56.

    Article  CAS  PubMed  Google Scholar 

  8. Fu X., Kao J.L.F., Bergt C., Kassim S.Y., Huq N.P., d’Avignon A., Parks W.C., Mecham R.P., Heinecke J.W. 2004. Oxidative cross-linking of tryptophan to glycine restrains matrix metalloproteinase activity: specific structural motifs control protein oxidation. J. Biol. Chem. 279, 6209–6212.

    Article  CAS  PubMed  Google Scholar 

  9. Nguyen-Khoa T., Massy Z.A., Witko-Sarsat V., Canteloup S., Kebede M., Lacour B., Drueke T., Descamps-Latscha B. 1999. Oxidized low-density lipoprotein induces macrophage respiratory burst via its protein moiety: A novel pathway in atherogenesis? Biochem. Biophys. Res. Commun. 263, 804–809.

    Article  CAS  PubMed  Google Scholar 

  10. Kopprasch S., Leonhardt W., Pietzsch J., Kuhne H. 1998. Hypochlorite-modified low-density lipoprotein stimulates human polymorphonuclear leukocytes for enhanced production of reactive oxygen metabolites, enzyme secretion, and adhesion to endothelial cells. Atherosclerosis. 136, 315–324.

    Article  CAS  PubMed  Google Scholar 

  11. Kopprasch S., Pietzsch J., Westendorf T., Kruse H.J., Grassler J. 2004. The pivotal role of scavenger receptor CD36 and phagocyte-derived oxidants in oxidized low density lipoprotein-induced adhesion to endothelial cells. Int. J. Biochem. Cell Biol. 36, 460–471.

    Article  CAS  PubMed  Google Scholar 

  12. Vicca S., Massy Z.A., Hennequin C., Rihane D., Drueke T.B., Lacour B. 2003. Apoptotic pathways involved in U937 cells exposed to LDL oxidized by hypochlorous acid. Free Radic. Biol. Med. 35, 603–615.

    Article  CAS  PubMed  Google Scholar 

  13. Arnhold J., Osipov A.N., Spalteholz H., Panasenko O.M., Schiller J. 2001. Effects of hypochlorous acid on unsaturated phosphatidylcholines. Free Radic. Biol. Med. 31, 1111–1119.

    Article  CAS  PubMed  Google Scholar 

  14. Panasenko O.M., Osipov A.N., Schiller J., Arnhold J. 2002. Interaction of exogenous hypochlorite and hypochlorite produced in the MPO+H2O2+Cl system with unsaturated phosphatidylcholine. Biokhimiya (Rus.). 67, 1071–1084 [Translated version: Biochemistry (Moscow). 67, 889–900].

    Google Scholar 

  15. Dever G.J., Benson R., Wainwright C.L., Kennedy S., Spickett C.M. 2008. Phospholipid chlorohydrin induces leukocyte adhesion to ApoE-/- mouse arteries via upregulation of P-selectin. Free Radic. Biol. Med. 44, 452–463.

    Article  CAS  PubMed  Google Scholar 

  16. Messner M.C., Albert C.J., McHowat J., Ford D.A. 2008. Identification of lysophosphatidylcholine-chlo rohydrin in human atherosclerotic lesions. Lipids. 43, 243–249.

    Article  CAS  PubMed  Google Scholar 

  17. Morris J.C. 1966. The acid ionization constant of HOCl from 5°C to 35°C. J. Phys. Chem. 70, 3798–3805.

    Article  CAS  Google Scholar 

  18. Kumar K., Margerum D.W. 1987. Kinetics and mechanism of general-acid-assisted oxidation of bromide by hypochlorite and hypochlorous acid. Inorg. Chem. 26, 2706–2711.

    Article  CAS  Google Scholar 

  19. Gazda M., Margeum D.W. 1994. Reactions of monochloramine with Br2, Br 3 , HOBr, and OBr 2 : Formation of bromochloramines. Inorg. Chem. 33, 118–123.

    Article  CAS  Google Scholar 

  20. Timoshenko A.V., Kayser K., Gabius H.J. 1998. Lectin-triggered superoxide/H2O2 and granule enzyme release from cells. Meth. Mol. Med. 9, 441–445.

    CAS  Google Scholar 

  21. Timoshenko A.V., Cherenkevich S.N. 1995. H2O2 generation and aggregation of human neutrophils as affected by lectins. Gematol. Transfuziol. 40, 32–35.

    CAS  PubMed  Google Scholar 

  22. Timoshenko A.V., Zorin V.P., Cherenkevich S.N. 1986. The influence of prostaglandins and inhibitors of arachidonic acid metabolism on Con A-induced agglutination of thymocytes. Abstracts of the All-Russian Symposium Synthesis and Analysis of Prostaglandins, Tallin, p. 169.

  23. Timoshenko A.V., Fomichev A.Yu., Cherenkevich S.N. 1994. The effect of metabolic inhibitors on stability of mannose-specific contacts of Escherichia coli K12 and human neutrophils. Gen. Mikrobiol. Virusol. 5, 9–13.

    Google Scholar 

  24. Timoshenko A.V., Gorudko I.V., Cherenkevich S.N., Gabius H.J. 1999. Differential potency of two crosslinking plant lectins to induce formation of haptenic-sugar-resistant aggregates of rat thymocytes by post-binding signaling. FEBS Lett. 449, 75–78.

    Article  CAS  PubMed  Google Scholar 

  25. Schiller J., Arnhold J., Benard S., Müller M., Reichl S., Arnold K. 1999. Lipid analysis by matrix-assisted laser desorption and ionization mass spectrometry: A methodological approach. Anal. Biochem. 267, 46–56.

    Article  CAS  PubMed  Google Scholar 

  26. Timoshenko A.V., Cherenkevich S.N., Samal A.B. 1986. The role of reactive oxygen species in concanavallin A-induced agglutination of lymphocytes. Vestn. Belorusskogo universiteta. Series 2, Chemistry, Biology, Geography, no. 3, 47–50.

  27. Lee S., Chung J., Ha I.S., Yi K., Lee J.E., Kang H.G., Choi I., Oh K.-H., Kim J.Y., Surh C.D., Ahn C. 2007. Hydrogen peroxide increases human leukocyte adhesion to porcine aortic endothelial cells via NFkB-dependent up-regulation of VCAM-1. Int. Immunol. 19, 1349–1359.

    Article  CAS  PubMed  Google Scholar 

  28. Nicholls S.J., Hazen S.L. 2009. Myeloperoxidase, modified lipoproteins and atherogenesis. J. Lipid Res. Suppl. 50,Suppl., S346–S351.

    Google Scholar 

  29. Esterbauer H., Wäg G., Puhl H. 1993. Lipid peroxidation and its role in atherosclerosis. Br. Med. Bull. 49, 566–576.

    CAS  PubMed  Google Scholar 

  30. Fontana L., Giagulli C., Cominacini L., Fratta Pasini A., Minuz P., Lechi A., Sala A., Laudanna C. 2002. β2 Integrin-dependent neutrophil adhesion induced by minimally modified low-density lipoproteins is mainly mediated by F2-isoprostanes. Circulation. 106, 2434–2441.

    Article  CAS  PubMed  Google Scholar 

  31. Dianzani C., Parrini M., Ferrara C., Fantozzi R. 1996. Effect of 4-hydroxynonenal on superoxide anion production from primed human neutrophils. Cell Biochem. Funct. 14, 193–200.

    Article  CAS  PubMed  Google Scholar 

  32. Sethi S., Eastman A.Y., Eaton J. W. 1996. Inhibition of phagocyte-endothelium interactions by oxidized fatty acids: A natural anti-inflammatory mechanism? J. Lab. Clin. Med. 128, 27–38.

    Article  CAS  PubMed  Google Scholar 

  33. Chen R., Chen X., Salomon R.G., McIntyre T.M. 2009. Platelet activation by low concentrations of intact oxidized LDL particles involves the PAF receptor. Arterioscler. Thromb. Vasc. Biol. 29, 363–371.

    Article  CAS  PubMed  Google Scholar 

  34. Leitinger N., Tyner T.R., Oslund L., Rizza C., Subbanagounder G., Lee H., Shih P.T., Mackman N., Tigyi G., Territo M.C., Berliner J.A., Vora D.K. 1999. Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils. Proc. Natl. Acad. Sci. USA. 96, 12010–12015.

    Article  CAS  PubMed  Google Scholar 

  35. Rouhanizadeh M., Hwang J., Clempus R.E., Marcu L., Lassegue B., Sevanian A., Hsiai T.K. 2005. Oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phospho-rylcholine induces vascular endothelial superoxide production: implication of NADPH oxidase. Free Radic. Biol. Med. 39, 1512–1522.

    Article  CAS  PubMed  Google Scholar 

  36. Malle E., Marsche G., Arnhold J., Davies M.J. 2006. Modification of low-density lipoprotein by myeloperoxidase-derived oxidants and reagent hypochlorous acid. Biochim. Biophys. Acta. 1761, 392–415.

    CAS  PubMed  Google Scholar 

  37. Panasenko O.M., Vakhrusheva T.V., Vlasova I.I., Chekanov A.V., Baranov Yu.V., Sergienko V.I. 2007. Role of myeloperoxidase-mediated modification of human blood lipoproteins in atherosclerosis development. Bull. Exp. Biol. Med. 144, 428–431.

    Article  CAS  PubMed  Google Scholar 

  38. Panasenko O.M., Spalteholz H., Schiller J., Arnhold J. 2003. Myeloperoxidase-induced formation of chlorohydrins and lysophospholipids from unsaturated phosphatidylcholines. Free Radic. Biol. Med. 34, 553–562.

    Article  CAS  PubMed  Google Scholar 

  39. Panasenko O.M., Spalteholz H., Schiller J., Arnhold J. 2006. Leukocytic myeloperoxidase-mediated formation of bromohydrins and lysophospholipids from unsaturated phosphatidylcholines. Biokhimiya (Rus.). 71, 707–718 [Translated version: Biochemistry (Moscow). 71, 571–580].

    Google Scholar 

  40. Condliffe A.M., Kitchen E., Chilvers E.R. 1998. Neutrophil priming: pathophysiological consequences and underlying mechanisms. Clin. Sci. 94, 461–471.

    CAS  PubMed  Google Scholar 

  41. Swain S.D., Rohn T.T., Quinn M.T. 2002. Neutrophil priming in host defense: Role of oxidants as priming agents. Antioxid. Redox Signal. 4, 69–83.

    Article  CAS  PubMed  Google Scholar 

  42. Spickett C.M. 2007. Chlorinated lipids and fatty acids: an emerging role in pathology. Pharmacol. Ther. 115, 400–409.

    Article  CAS  PubMed  Google Scholar 

  43. Dever G., Wainwright C.L., Kennedy S., Spickett, C.M. 2006. Fatty acid and phospholipid chlorohydrins cause cell stress and endothelial adhesion. Acta Biochim. Pol. 53, 761–768.

    CAS  PubMed  Google Scholar 

  44. Marsche G., Heller R., Fauler G., Kovacevic, A., Nuszkowski A., Graier W., Sattler W., Malle E. 2004. 2-Chlorohexadecanal derived from hypochlorite-modified high-density lipoprotein-associated plasmalogen is a natural inhibitor of endothelial nitric oxide biosynthesis. Arterioscler. Thromb. Vasc. Biol. 24, 2302–2306.

    Article  CAS  PubMed  Google Scholar 

  45. Podrez E.A., Poliakov E., Shen Z., Zhang R., Deng Y., Sun M., Finton P.J., Shan L., Gugiu B., Fox P.L., Hoff H.F., Salomon R.G., Hazen S.L. 2002. Identification of a novel family of oxidized phospholipids that serve as ligands for the macrophage scavenger receptor CD36. J. Biol. Chem. 277, 38503–38516.

    Article  CAS  PubMed  Google Scholar 

  46. Moore K.J., Freeman M.W. 2006. Scavenger receptors in atherosclerosis: Beyond lipid uptake. Arterioscler. Thromb. Vasc. Biol. 26, 1702–1711.

    Article  CAS  PubMed  Google Scholar 

  47. Moumtzi A., Trenker M., Flicker K., Zenzmaier E., Saf R., Hermetter A. 2007. Import and fate of fluorescent analogs of oxidized phospholipids in vascular smooth muscle cells. J. Lipid Res. 48, 565–582.

    Article  CAS  PubMed  Google Scholar 

  48. Rhode S., Grurl R., Brameshuber M., Hermetter A., Schütz G.J. 2009. Plasma membrane fluidity affects transient immobilization of oxidized phospholipids in endocytotic sites for subsequent uptake. J. Biol. Chem. 284, 2258–2265.

    Article  CAS  PubMed  Google Scholar 

  49. Shao D., Segal A.W., Dekker L.V. 2003. Lipid rafts determine efficiency of NADPH oxidase activation in neutrophils. FEBS Lett. 550, 101–106.

    Article  CAS  PubMed  Google Scholar 

  50. Sitrin R.G., Emery S.L., Sassanella T.M., Blackwood R.A., Petty H.R. 2006. Selective localization of recognition complexes for leukotriene B4 and formyl-Met-Leu-Phe within lipid raft microdomains of human polymorphonuclear neutrophils. J. Immunol. 177, 8177–8184.

    CAS  PubMed  Google Scholar 

  51. Carr A.C., Vissers M.C., Domigan N.M., Winterbourn C.C. 1997. Modification of red cell membrane lipids by hypochlorous acid and haemolysis by preformed lipid chlorohydrins. Redox Rep. 3, 263–271.

    CAS  PubMed  Google Scholar 

  52. Gorudko I.V., Buko I.V., Cherenkevich S.N., Polonetsky L.Z., Timoshenko A.V. 2008. Lectin-induced aggregates of blood cells from patients with acute coronary syndromes. Arch. Med. Res. 39, 674–681.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to I. V. Gorudko.

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Original Russian Text © I.V. Gorudko, T.V. Vakhrusheva, A.V. Mukhortova, S.N. Cherenkevich, A.V. Timoshenko, V.I. Sergienko, O.M. Panasenko, 2010, published in Biologicheskie Membrany, 2010, Vol. 27, No. 4, pp. 314–324.

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Gorudko, I.V., Vakhrusheva, T.V., Mukhortova, A.V. et al. The priming effect of halogenated phospholipids on the functional responses of human neutrophils. Biochem. Moscow Suppl. Ser. A 4, 262–271 (2010). https://doi.org/10.1134/S1990747810030037

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