Skip to main content
Log in

Activation of T-Lymphocytes by LDL-Cholesterol

  • Original Article
  • Published:
Lipids

Abstract

Native LDL-cholesterol can be mechanically stressed by strong vortexing. According to one hypothesis, mechanical shear stress within the vessel can lead to an aggregation of LDL-cholesterol and subsequently to activation of CD4 and CD8 T-lymphocytes. The goal of this study was to determine the proportion of activated CD4 and CD8 T-lymphocytes that is induced by adding unstressed and mechanically stressed LDL-cholesterol to whole blood samples. Whole blood was taken from 12 healthy subjects. All probands fasted for at least 12 h before blood withdrawal. In each case, 1 ml of whole blood from each subject was incubated for 16 h at 32 °C (89.3 °F) with concanavalin A (A), without additive (B), with mechanically stressed LDL-cholesterol (C) or with native LDL-cholesterol (D). Subsequently, the samples were measured by four-color flow cytometry. CD3, CD4, CD8, and CD69 were measured as activity markers. CD69 was plotted against CD4 and CD8, and the proportions of activated CD4 and CD8 T-lymphocytes were determined. Native and vortexed LDL-cholesterol elicited significantly different types of T-cell activation. While native LDL activated CD4 T-cells to only a small extent, mechanically stressed (vortexed) LDL potently activated CD8 T-cells. Purely mechanically-induced changes in LDL-cholesterol may be one mechanism that contributes to the activation of CD8 cells and, as a consequence, the emergence of arteriosclerosis.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Arneth B (2003) Theory of mechanical immunology. J Mech Med Biol 3:285–297

    Article  Google Scholar 

  2. Vinereanu D (2006) Risk factors for atherosclerotic disease: present and future. Herz 31(Suppl 3):5–24

    PubMed  Google Scholar 

  3. von Eckardstein A (2005) Risk factors for atherosclerotic vascular disease. Handb Exp Pharmacol 170:71–105

    Article  Google Scholar 

  4. Braunwald E (2005) Approach to the patient with cardiovascular disease. In: Kasper DL, Braunwald E et al (eds) Harrison's principles of internal medicine, 16th edn. McGraw Hill, New York, pp 1358–1367

    Google Scholar 

  5. Kannel WB, Castelli WP, Gordon T, McNamara PM (1971) Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Ann Intern Med 1:1–12

    Google Scholar 

  6. Torzewski M, Suriyaphol P, Paprotka K, Spath L, Ochsenhirt V, Schmitt A, Han SR, Husmann M, Gerl VB, Bhakdi S, Lackner KJ (2004) Enzymatic modification of low-density lipoprotein in the arterial wall: a new role for plasmin and matrix metalloproteinases in atherogenesis. Arterioscler Thromb Vasc Biol 11:2130–2136

    Article  Google Scholar 

  7. Murphy KM, Travers P, Walport M (2008) Janeway′s immunobiology. 7th edn. Garland Sciences, New york

  8. Talbot RM, del Rio JD, Weinberg PD (2003) Effect of fluid mechanical stresses and plasma constituents on aggregation of LDL. J Lipid Res 44:837–845

    Article  PubMed  CAS  Google Scholar 

  9. Khoo JC, Miller E, McLoughlin P, Steinberg D (1988) Enhanced macrophage uptake of low density lipoprotein after self-aggregation. Arteriosclerosis 8:348–358

    PubMed  CAS  Google Scholar 

  10. Khoo JC, Miller E, McLoughlin P, Steinberg D (1990) Prevention of low density lipoprotein aggregation by high density lipoprotein or apolipoprotein A-1. J Lipid Res 31:645–652

    PubMed  CAS  Google Scholar 

  11. Hughes RE, Maton SC (1968) The passage of vitamin C across the erythrocyte membrane. Br J Haematol 14:247–253

    Article  PubMed  CAS  Google Scholar 

  12. Lohmann W (1983) Structure of ascorbic acid and its biological function. Eur Biophys J 10:205–210

    Google Scholar 

  13. Li S, Schoneich C, Wilson GS, Borchardt RT (1993) Chemical pathways of peptide degradation. Ascorbic acid promotes rather than inhibits the oxidation of methionine to methionine sulfoxide in small model peptides. Pharm Res 10:1572–1579

    Article  PubMed  CAS  Google Scholar 

  14. Haeffner F, Smith DG, Barnham KJ, Bush AI (2005) Model studies of cholesterol and ascorbate oxidation by copper complexes: relevance to Alzheimer’s disease beta-amyloid metallochemistry. J Inorg Biochem 99:2403–2422

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Borros Arneth.

About this article

Cite this article

Arneth, B. Activation of T-Lymphocytes by LDL-Cholesterol. Lipids 44, 311–316 (2009). https://doi.org/10.1007/s11745-008-3273-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-008-3273-3

Keywords

Navigation