Skip to main content
Log in

The protective effects of HDL and its constitutents against neutrophil respiratory burst activation by hypochlorite-oxidized LDL

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Hypochlorite-oxidized low-density lipoprotein (oxLDL) possesses a substantial proinflammatory potential by modulating respiratory burst activities of polymorphonuclear neutrophils (PMN). As evaluated by luminol-amplified chemiluminescence (CL) incubation of 106 PMN/ml with 70 nM oxLDL was followed by substantial induction of neutrophil oxidant (ROS) generation. We evaluated the inhibitory capacity of high-density lipoprotein (HDL) and its lipid and protein constituents against the activating effects of oxLDL. At a HDL or apolipoprotein AI/LDL protein ratio of 1.0, native HDL decreased the respiratory burst activation by 64%, followed by trypsinized HDL (57%) and native apoAI (43%). The inhibitory effects of native HDL did not require prior incubation with PMN or with oxLDL suggesting an instantaneously acting protective mechanism in the minute range. OxLDL modulated ROS production not only of resting PMN but also that of activated PMN, as indicated by a 14-fold increase in FMLP-stimulated CL response and a 50% decrease in zymosan-mediated CL answer. HDL itself did not protect PMN from activation by FMLP and zymosan. However, it clearly reduced effects of oxLDL on FMLP-activation and slightly counteracted the oxLDL-mediated decrease in zymosan-induced ROS generation. Taken together, these findings may offer new insight into atheroprotective mechanisms of HDL.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Steinberg D: Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272: 20963–20966, 1997

    Google Scholar 

  2. Carr A, McCall MR, Frei B: Oxidation of LDL by myeloperoxidase and reactive nitrogen species. Arterioscler Thromb Vasc Biol 20: 1716–1723, 2000

    Google Scholar 

  3. Hazell LJ, Stocker R: Oxidation of low-density lipoprotein with hypochlorite causes transformation of the lipoprotein into a high-uptake form for macrophages. Biochem J 290: 165–172, 1993

    Google Scholar 

  4. Kopprasch S, Leonhardt W, Pietzsch J, Kühne H: 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, 1998

    Google Scholar 

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

    Google Scholar 

  6. Nuszkowski A, Grabner R, Marsche G, Unbehaun A, Malle E, Heller R: Hypochlorite-modified low density lipoprotein inhibits nitric oxide synthesis in endothelial cells via an intracellular dislocalization of endothelial nitric-oxide synthase. J Biol Chem 276: 14212–14221, 2001

    Google Scholar 

  7. Hörkkö S, Binder CJ, Shaw PX, Chang MK, Silverman G, Palinski W, Witztum JL: Immunological responses to oxidized LDL. Free Rad Biol Med 28: 1771–1779, 2000

    Google Scholar 

  8. Kopprasch S, Pietzsch J, Kuhlisch E, Fuecker K, Temelkova-Kurktschiev T, Hanefeld M, Kühne H, Julius U, Graessler J: In vivo evidence for increased oxidation of circulating LDL in impaired glucose tolerance. Diabetes 51: 3102–3106, 2002

    Google Scholar 

  9. Pietzsch J, Lattke P, Julius U: Oxidation of apolipoprotein B-100 in circulating LDL is related to LDL residence time. Arterioscler Thromb Vasc Biol 20: e63–e67, 2000

    Google Scholar 

  10. Holvoet P, Mertens A, Verhamme P, Bogaerts K, Beyens G, Verhaeghe R, Collen D, Muls E, Van de Werf F: Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol 21: 844–848, 2001

    Google Scholar 

  11. Frei B, Stocker R, Ames BN: Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci USA 85: 9748–9752, 1988

    Google Scholar 

  12. Brown MS, Ho YK, Goldstein JL: The cholesteryl ester cycle in macrophage foam cells. Continual hydrolysis and re-esterification of cytoplasmic cholesteryl esters. J Biol Chem 255: 9344–9352, 1980

    Google Scholar 

  13. Sangvanich P, Mackness B, Gaskell SJ, Durrington P, Mackness M: The effect of high-density lipoproteins on the formation of lipid/protein conjugates during in vitro oxidation of low-density lipoprotein. Biochem Biophys Res Commun 300: 501–506, 2003

    Google Scholar 

  14. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, Navab M: Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 96: 2882–2891, 1995

    Google Scholar 

  15. Garner B, Waldeck R, Witting PK, Rye KA, Stocker R: Oxidation of high density lipoproteins. J Biol Chem 273: 6088–6095, 1998

    Google Scholar 

  16. Johansson J, Carlson LA, Landou C, Hamsten A: High density lipoproteins and coronary atherosclerosis. A strong inverse relation with the largest particles is confined to normotriglyceridemic patients. Arterioscler Thromb 11: 174–182, 1991

    Google Scholar 

  17. Pietzsch J, Subat S, Nitzsche S, Leonhardt W, Schentke KU, Hanefeld M: Very fast ultracentrifugation of serum lipoproteins: Influence on lipoprotein separation and composition. Biochim Biophys Acta 1254: 77–88, 1995

    Google Scholar 

  18. Scanu AM, Edelstein C: Solubility in aqueous solutions of ethanol of the small molecular weight peptides of the serum very low density and high density lipoproteins: Relevance to the recovery problem during delipidation of serum lipoproteins. Anal Biochem 44: 576–588, 1971

    Google Scholar 

  19. Matsuda YK, Hirata K, Inoue N, Suematsu M, Kawashima S, Akita H, Yokoyama M: High density lipoprotein reverses inhibitory effect of oxidized low density lipoprotein on endothelium-dependent arterial relaxation. Circ Res 72: 1103–1109, 1993

    Google Scholar 

  20. Uittenbogaard A, Shaul PW, Yuhanna IS, Blair A, Smart EJ: High density lipoprotein prevents oxidized low density lipoprotein-induced inhibition of endothelial nitric-oxide synthase localization and activation in caveolae. J Biol Chem 275: 11278–11283, 2000

    Google Scholar 

  21. Sakai M, Miyazaki A, Hakamata H, Sasaki T, Yui S, Yamazaki M, Shichiri M, Horiuchi S: Lysophosphatidylcholine plays an essential role in the mitogenic effect of oxidized low density lipoprotein on murine macrophages. J Biol Chem 269: 31430–31435, 1994

    Google Scholar 

  22. Suc I, Escargueil-Blanc I, Troly M, Salvayre R, Negre-Salvayre A: HDL and ApoA prevent cell death of endothelial cells induced by oxidized LDL. Arterioscler Thromb Vasc Biol 17: 2158–2166, 1997

    Google Scholar 

  23. Nilsson J, Dahlgren B, Ares M, Westman J, Hultgardh Nilsson A, Cercek B, Shah PK: Lipoprotein-like phospholipid particles inhibit the smooth muscle cell cytotoxicity of lysophosphatidylcholine and platelet-activating factor. Arterioscler Thromb Vasc Biol 18: 13–19, 1998

    Google Scholar 

  24. Nisihoka H, Horiuchi H, Arai H, Kita T: Lysophosphatidylcholine generates superoxide anions through activation of phosphatidylinositol 3-kinase in human neutrophils. FEBS Lett 441: 63–66, 1998

    Google Scholar 

  25. Blackburn WD, Dohlman JG, Venkatachalapathi YV, Pillion DJ, Koopman WJ, Segrest JP, Anantharamaiah GM: Apolipoprotein A-I decreases neutrophil degranulation and superoxide production. J Lipid Res 32: 1911–1918, 1991

    Google Scholar 

  26. Kopprasch S, Gatzweiler A, Graessler J, Schröder HE: Beta-adrenergic modulation of FMLP-and zymosan-induced intracellular and extracellular oxidant production by polymorphonuclear leukocytes. Mol Cell Biochem 168: 133–139, 1997

    Google Scholar 

  27. Karlsson A, Nixon JB, McPhail LC: Phorbol myristate acetate induces neutrophil NADPH-oxidase activity by two separate pathways: Dependent or independent of phosphatidylinositol 3-kinase. J Leukocyte Biol 67: 396–404, 2000

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kopprasch, S., Pietzsch, J. & Graessler, J. The protective effects of HDL and its constitutents against neutrophil respiratory burst activation by hypochlorite-oxidized LDL. Mol Cell Biochem 258, 121–127 (2004). https://doi.org/10.1023/B:MCBI.0000012842.19059.c5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:MCBI.0000012842.19059.c5

Navigation