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
. 1986 Apr;83(8):2704–2708. doi: 10.1073/pnas.83.8.2704

The role of lipoproteins and receptor-mediated endocytosis in the transport of bacterial lipopolysaccharide.

B J Van Lenten, A M Fogelman, M E Haberland, P A Edwards
PMCID: PMC323368  PMID: 3517876

Abstract

The addition of bacterial lipopolysaccharide (LPS) from Escherichia coli 0111:B4 to human monocyte-macrophages cultured in serum results in suppression of scavenger receptor activity. The present studies were performed to examine if the effect on scavenger receptor activity was mediated by LPS alone or by LPS in association with lipoproteins. Radioiodinated LPS (125I-LPS) was added to human plasma in vitro and to normal and hyperlipidemic rabbit plasma in vitro and in vivo to determine the distribution of 125I-LPS among the lipoprotein classes. It was found that all lipoprotein classes bound LPS in direct proportion to their plasma cholesterol concentration. LPS alone was compared to LPS bound to low density lipoprotein (LDL), high density lipoprotein, or reductively-methylated LDL for their abilities to suppress scavenger receptor activity in monocyte-macrophages in lipoprotein-free serum. Only LPS bound to LDL (LPS-LDL) demonstrated an effect similar to that observed when LPS was added to cells in serum. Either unlabeled LDL or unlabeled LPS-LDL complexes competed with the uptake of 125I-LPS-LDL complexes, which appeared to proceed by receptor-mediated endocytosis. In contrast to the uptake of 125I-LDL, the uptake of 125I-LPS-LDL by cultured monocyte-macrophages was not followed by its hydrolysis and the release of its radioactive degradation products into the medium. The association of LPS with lipoproteins was very stable and appeared to be mediated by a lipid-lipid interaction. We hypothesize that LPS bound to lipoproteins may be transported into the artery wall and may initiate the atherosclerotic reaction.

Full text

PDF
2704

Selected References

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

  1. Bhakdi S., Tranum-Jensen J., Utermann G., Füssle R. Binding and partial inactivation of Staphylococcus aureus alpha-toxin by human plasma low density lipoprotein. J Biol Chem. 1983 May 10;258(9):5899–5904. [PubMed] [Google Scholar]
  2. Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
  3. Duncan R. L., Jr, Morrison D. C. The fate of E. coli lipopolysaccharide after the uptake of E. coli by murine macrophages in vitro. J Immunol. 1984 Mar;132(3):1416–1424. [PubMed] [Google Scholar]
  4. Goldstein J. L., Brown M. S. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem. 1974 Aug 25;249(16):5153–5162. [PubMed] [Google Scholar]
  5. Gordon T., Castelli W. P., Hjortland M. C., Kannel W. B., Dawber T. R. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977 May;62(5):707–714. doi: 10.1016/0002-9343(77)90874-9. [DOI] [PubMed] [Google Scholar]
  6. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Haberland M. E., Olch C. L., Folgelman A. M. Role of lysines in mediating interaction of modified low density lipoproteins with the scavenger receptor of human monocyte macrophages. J Biol Chem. 1984 Sep 25;259(18):11305–11311. [PubMed] [Google Scholar]
  8. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  9. Labischinski H., Barnickel G., Bradaczek H., Naumann D., Rietschel E. T., Giesbrecht P. High state of order of isolated bacterial lipopolysaccharide and its possible contribution to the permeation barrier property of the outer membrane. J Bacteriol. 1985 Apr;162(1):9–20. doi: 10.1128/jb.162.1.9-20.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lee D. M., Alaupovic P. Physiocochemical properties of low-density lipoproteins of normal human plasma. Evidence for the occurrence of lipoprotein B in associated and free forms. Biochem J. 1974 Feb;137(2):155–167. doi: 10.1042/bj1370155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. McFARLANE A. S. Efficient trace-labelling of proteins with iodine. Nature. 1958 Jul 5;182(4627):53–53. doi: 10.1038/182053a0. [DOI] [PubMed] [Google Scholar]
  12. Morrison D. C., Ulevitch R. J. The effects of bacterial endotoxins on host mediation systems. A review. Am J Pathol. 1978 Nov;93(2):526–618. [PMC free article] [PubMed] [Google Scholar]
  13. Munford R. S., Andersen J. M., Dietschy J. M. Sites of tissue binding and uptake in vivo of bacterial lipopolysaccharide-high density lipoprotein complexes: studies in the rat and squirrel monkey. J Clin Invest. 1981 Dec;68(6):1503–1513. doi: 10.1172/JCI110404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Phelan J. P., Van Lenten B. J., Fogelman A. M., Kean C., Haberland M. E., Edwards P. A. Notes on the breeding of the WHHL rabbit: an animal model of familial hypercholesterolemia. J Lipid Res. 1985 Jun;26(6):776–778. [PubMed] [Google Scholar]
  15. Ross R. George Lyman Duff Memorial Lecture. Atherosclerosis: a problem of the biology of arterial wall cells and their interactions with blood components. Arteriosclerosis. 1981 Sep-Oct;1(5):293–311. doi: 10.1161/01.atv.1.5.293. [DOI] [PubMed] [Google Scholar]
  16. Shechter I., Fogelman A. M., Haberland M. E., Seager J., Hokom M., Edwards P. A. The metabolism of native and malondialdehyde-altered low density lipoproteins by human monocyte-macrophages. J Lipid Res. 1981 Jan;22(1):63–71. [PubMed] [Google Scholar]
  17. Smith E. B., Staples E. M. Distribution of plasma proteins across the human aortic wall--barrier functions of endothelium and internal elastic lamina. Atherosclerosis. 1980 Dec;37(4):579–590. doi: 10.1016/0021-9150(80)90065-9. [DOI] [PubMed] [Google Scholar]
  18. Ulevitch R. J., Johnston A. R. The modification of biophysical and endotoxic properties of bacterial lipopolysaccharides by serum. J Clin Invest. 1978 Dec;62(6):1313–1324. doi: 10.1172/JCI109252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ulevitch R. J., Johnston A. R., Weinstein D. B. New function for high density lipoproteins. Isolation and characterization of a bacterial lipopolysaccharide-high density lipoprotein complex formed in rabbit plasma. J Clin Invest. 1981 Mar;67(3):827–837. doi: 10.1172/JCI110100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ulevitch R. J., Johnston A. R., Weinstein D. B. New function for high density lipoproteins. Their participation in intravascular reactions of bacterial lipopolysaccharides. J Clin Invest. 1979 Nov;64(5):1516–1524. doi: 10.1172/JCI109610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ulevitch R. J. The preparation and characterization of a radioiodinated bacterial lipopolysaccharide. Immunochemistry. 1978 Mar;15(3):157–164. doi: 10.1016/0161-5890(78)90144-x. [DOI] [PubMed] [Google Scholar]
  22. Van Lenten B. J., Fogelman A. M., Seager J., Ribi E., Haberland M. E., Edwards P. A. Bacterial endotoxin selectively prevents the expression of scavenger-receptor activity on human monocyte-macrophages. J Immunol. 1985 Jun;134(6):3718–3721. [PubMed] [Google Scholar]
  23. Wiklund O., Carew T. E., Steinberg D. Role of the low density lipoprotein receptor in penetration of low density lipoprotein into rabbit aortic wall. Arteriosclerosis. 1985 Mar-Apr;5(2):135–141. doi: 10.1161/01.atv.5.2.135. [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