Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 May;80(9):2757–2761. doi: 10.1073/pnas.80.9.2757

Nonenzymatic glucosylation of homologous low density lipoprotein and albumin renders them immunogenic in the guinea pig.

J L Witztum, U P Steinbrecher, M Fisher, A Kesaniemi
PMCID: PMC393907  PMID: 6405389

Abstract

Nonenzymatic glucosylation of low density lipoprotein (LDL) and other plasma and structural proteins is enhanced in diabetics. Because conjugated carbohydrates are known to play an important role in the immunogenicity of proteins, we sought to determine if glucosylation of LDL (yielding Glc-LDL) and albumin would make them immunogenic. Therefore, we immunized guinea pigs with homologous glucosylated proteins and measured antibody response by solid-phase radioimmunoassay. Glucosylation of LDL in the presence of cyanoborohydride yields glucitol-lysine as the glucose adduct. Immunization with this Glc-LDL yielded a high-titered antiserum that reacted specifically with guinea pig Glc-LDL but not native LDL. Glucitol-lysine was an effective competitor for binding to the antibody, as were other reductively glucosylated human proteins. Glucosylation of LDL by incubation with glucose in the absence of a reducing agent yields fructosyllysine as the glucose adduct. This product, which has been demonstrated in human plasma, was also immunogenic, though the antiserum produced was of lower titer and affinity. Homologous glucosylated albumin was also immunogenic. These data suggest that nonenzymatic glucosylation of proteins could lead to autoantibody production and the formation of immune complexes in diabetic plasma and tissues.

Full text

PDF
2757

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bauer B. J., Blashfield K., Norris R., Buthala D. A., Ginsberg L. C. Immunoglobulin as the major low density lipoprotein binding protein in plasma. Atherosclerosis. 1982 Aug;44(2):153–160. doi: 10.1016/0021-9150(82)90110-1. [DOI] [PubMed] [Google Scholar]
  2. Bodansky H. J., Wolf E., Cudworth A. G., Dean B. M., Nineham L. J., Bottazzo G. F., Matthews J. A., Kurtz A. B., Kohner E. M. Genetic and immunologic factors in microvascular disease in type I insulin-dependent diabetes. Diabetes. 1982 Jan;31(1):70–74. doi: 10.2337/diab.31.1.70. [DOI] [PubMed] [Google Scholar]
  3. Bunn H. F., Gabbay K. H., Gallop P. M. The glycosylation of hemoglobin: relevance to diabetes mellitus. Science. 1978 Apr 7;200(4337):21–27. doi: 10.1126/science.635569. [DOI] [PubMed] [Google Scholar]
  4. Curtiss L. K., Edgington T. S. Immunochemical heterogeneity of human plasma apolipoprotein B. I. Apolipoprotein B binding of mouse hybridoma antibodies. J Biol Chem. 1982 Dec 25;257(24):15213–15221. [PubMed] [Google Scholar]
  5. Higgins P. J., Bunn H. F. Kinetic analysis of the nonenzymatic glycosylation of hemoglobin. J Biol Chem. 1981 May 25;256(10):5204–5208. [PubMed] [Google Scholar]
  6. Iavicoli M., Di Mario U., Pozzilli P., Canalese J., Ventriglia L., Galfo C., Andreani D. Impaired phagocytic function and increased immune complexes in diabetics with severe microangiopathy. Diabetes. 1982 Jan;31(1):7–11. doi: 10.2337/diab.31.1.7. [DOI] [PubMed] [Google Scholar]
  7. Irvine W. J., Di Mario U., Guy K., Iavicoli M., Pozzilli P., Lumbroso B., Andreani D. Immune complexes and diabetic microangiopathy. J Clin Lab Immunol. 1978 Nov;1(3):187–191. [PubMed] [Google Scholar]
  8. Mauer S. M., Michael A. F., Fish A. J., Brown D. M. Spontaneous immunoglobulin and complement deposition in glomeruli of diabetic rats. Lab Invest. 1972 Nov;27(5):488–494. [PubMed] [Google Scholar]
  9. Plow E. F., Edgington T. S. Immune responses to the cleavage-associated neoantigens of fibrinogen in man. Identification and characterization of humoral antibodies specific for cleavage fragments. J Clin Invest. 1975 Dec;56(6):1509–1518. doi: 10.1172/JCI108232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Trivelli L. A., Ranney H. M., Lai H. T. Hemoglobin components in patients with diabetes mellitus. N Engl J Med. 1971 Feb 18;284(7):353–357. doi: 10.1056/NEJM197102182840703. [DOI] [PubMed] [Google Scholar]
  11. Wardle E. N. An antibody to low density lipoprotein in diabetics. Experientia. 1978 Jul 15;34(7):886–887. doi: 10.1007/BF01939684. [DOI] [PubMed] [Google Scholar]
  12. Witztum J. L., Mahoney E. M., Branks M. J., Fisher M., Elam R., Steinberg D. Nonenzymatic glucosylation of low-density lipoprotein alters its biologic activity. Diabetes. 1982 Apr;31(4 Pt 1):283–291. doi: 10.2337/diab.31.4.283. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES