Skip to main content
NCBI 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
. 1992 Nov 1;89(21):10375–10379. doi: 10.1073/pnas.89.21.10375

Macrophages in Drosophila embryos and L2 cells exhibit scavenger receptor-mediated endocytosis.

J M Abrams 1, A Lux 1, H Steller 1, M Krieger 1
PMCID: PMC50341  PMID: 1438223

Abstract

Mammalian macrophage scavenger receptors exhibit unusually broad binding specificity and are implicated in atherosclerosis and host defense. Scavenger receptor-like endocytosis was observed in Drosophila melanogaster embryos and in primary embryonic cell cultures. This receptor activity was expressed primarily by macrophages. The Drosophila Schneider L2, but not the Kc, cell line also exhibited a scavenger receptor-mediated endocytic pathway similar to its mammalian counterpart. L2 receptors mediated high-affinity internalization and subsequent temperature- and chloroquine-sensitive degradation of 125I-labeled acetylated low density lipoprotein and displayed characteristic ligand specificity. These findings suggest that scavenger receptors mediate important, well-conserved functions and raise the possibility that they may be pattern recognition receptors that arose early in the evolution of host defense mechanisms. They also establish additional systems for the investigation of endocytosis in Drosophila and scavenger receptor function in disease, host defense, and development.

Full text

PDF
10375

Images in this article

10376Image
on p.10376
10376Image
on p.10376
10377Image
on p.10377
10378Image
on p.10378

Selected References

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

  1. Brehélin M. Comparative study of structure and function of blood cells from two Drosophila species. Cell Tissue Res. 1982;221(3):607–615. doi: 10.1007/BF00215704. [DOI] [PubMed] [Google Scholar]
  2. Brown M. S., Goldstein J. L. Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis. Annu Rev Biochem. 1983;52:223–261. doi: 10.1146/annurev.bi.52.070183.001255. [DOI] [PubMed] [Google Scholar]
  3. DiMario P. J., Mahowald A. P. Female sterile (1) yolkless: a recessive female sterile mutation in Drosophila melanogaster with depressed numbers of coated pits and coated vesicles within the developing oocytes. J Cell Biol. 1987 Jul;105(1):199–206. doi: 10.1083/jcb.105.1.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ezekowitz R. A., Williams D. J., Koziel H., Armstrong M. Y., Warner A., Richards F. F., Rose R. M. Uptake of Pneumocystis carinii mediated by the macrophage mannose receptor. Nature. 1991 May 9;351(6322):155–158. doi: 10.1038/351155a0. [DOI] [PubMed] [Google Scholar]
  5. Fessler J. H., Fessler L. I. Drosophila extracellular matrix. Annu Rev Cell Biol. 1989;5:309–339. doi: 10.1146/annurev.cb.05.110189.001521. [DOI] [PubMed] [Google Scholar]
  6. Freeman M., Ashkenas J., Rees D. J., Kingsley D. M., Copeland N. G., Jenkins N. A., Krieger M. An ancient, highly conserved family of cysteine-rich protein domains revealed by cloning type I and type II murine macrophage scavenger receptors. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8810–8814. doi: 10.1073/pnas.87.22.8810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Freeman M., Ekkel Y., Rohrer L., Penman M., Freedman N. J., Chisolm G. M., Krieger M. Expression of type I and type II bovine scavenger receptors in Chinese hamster ovary cells: lipid droplet accumulation and nonreciprocal cross competition by acetylated and oxidized low density lipoprotein. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4931–4935. doi: 10.1073/pnas.88.11.4931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goldstein J. L., Basu S. K., Brown M. S. Receptor-mediated endocytosis of low-density lipoprotein in cultured cells. Methods Enzymol. 1983;98:241–260. doi: 10.1016/0076-6879(83)98152-1. [DOI] [PubMed] [Google Scholar]
  9. Goldstein J. L., Brown M. S., Anderson R. G., Russell D. W., Schneider W. J. Receptor-mediated endocytosis: concepts emerging from the LDL receptor system. Annu Rev Cell Biol. 1985;1:1–39. doi: 10.1146/annurev.cb.01.110185.000245. [DOI] [PubMed] [Google Scholar]
  10. Goldstein J. L., Ho Y. K., Basu S. K., Brown M. S. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. Proc Natl Acad Sci U S A. 1979 Jan;76(1):333–337. doi: 10.1073/pnas.76.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gordon S., Perry V. H., Rabinowitz S., Chung L. P., Rosen H. Plasma membrane receptors of the mononuclear phagocyte system. J Cell Sci Suppl. 1988;9:1–26. doi: 10.1242/jcs.1988.supplement_9.1. [DOI] [PubMed] [Google Scholar]
  12. Hampton R. Y., Golenbock D. T., Penman M., Krieger M., Raetz C. R. Recognition and plasma clearance of endotoxin by scavenger receptors. Nature. 1991 Jul 25;352(6333):342–344. doi: 10.1038/352342a0. [DOI] [PubMed] [Google Scholar]
  13. Janeway C. A., Jr The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol Today. 1992 Jan;13(1):11–16. doi: 10.1016/0167-5699(92)90198-G. [DOI] [PubMed] [Google Scholar]
  14. Kessell I., Holst B. D., Roth T. F. Membranous intermediates in endocytosis are labile, as shown in a temperature-sensitive mutant. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4968–4972. doi: 10.1073/pnas.86.13.4968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kingsley D. M., Krieger M. Receptor-mediated endocytosis of low density lipoprotein: somatic cell mutants define multiple genes required for expression of surface-receptor activity. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5454–5458. doi: 10.1073/pnas.81.17.5454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kodama T., Freeman M., Rohrer L., Zabrecky J., Matsudaira P., Krieger M. Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. Nature. 1990 Feb 8;343(6258):531–535. doi: 10.1038/343531a0. [DOI] [PubMed] [Google Scholar]
  17. Koenig J. H., Ikeda K. Transformational process of the endosomal compartment in nephrocytes of Drosophila melanogaster. Cell Tissue Res. 1990 Nov;262(2):233–244. doi: 10.1007/BF00309878. [DOI] [PubMed] [Google Scholar]
  18. Krieger M. Molecular flypaper and atherosclerosis: structure of the macrophage scavenger receptor. Trends Biochem Sci. 1992 Apr;17(4):141–146. doi: 10.1016/0968-0004(92)90322-z. [DOI] [PubMed] [Google Scholar]
  19. Krämer H., Cagan R. L., Zipursky S. L. Interaction of bride of sevenless membrane-bound ligand and the sevenless tyrosine-kinase receptor. Nature. 1991 Jul 18;352(6332):207–212. doi: 10.1038/352207a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Lee K. J., Freeman M., Steller H. Expression of the disconnected gene during development of Drosophila melanogaster. EMBO J. 1991 Apr;10(4):817–826. doi: 10.1002/j.1460-2075.1991.tb08014.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nishikawa K., Arai H., Inoue K. Scavenger receptor-mediated uptake and metabolism of lipid vesicles containing acidic phospholipids by mouse peritoneal macrophages. J Biol Chem. 1990 Mar 25;265(9):5226–5231. [PubMed] [Google Scholar]
  23. Rohrer L., Freeman M., Kodama T., Penman M., Krieger M. Coiled-coil fibrous domains mediate ligand binding by macrophage scavenger receptor type II. Nature. 1990 Feb 8;343(6258):570–572. doi: 10.1038/343570a0. [DOI] [PubMed] [Google Scholar]
  24. Steinberg D., Parthasarathy S., Carew T. E., Khoo J. C., Witztum J. L. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989 Apr 6;320(14):915–924. doi: 10.1056/NEJM198904063201407. [DOI] [PubMed] [Google Scholar]
  25. Steller H., Fischbach K. F., Rubin G. M. Disconnected: a locus required for neuronal pathway formation in the visual system of Drosophila. Cell. 1987 Sep 25;50(7):1139–1153. doi: 10.1016/0092-8674(87)90180-2. [DOI] [PubMed] [Google Scholar]
  26. Steller H., Pirrotta V. Regulated expression of genes injected into early Drosophila embryos. EMBO J. 1984 Jan;3(1):165–173. doi: 10.1002/j.1460-2075.1984.tb01778.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Taylor M. E., Bezouska K., Drickamer K. Contribution to ligand binding by multiple carbohydrate-recognition domains in the macrophage mannose receptor. J Biol Chem. 1992 Jan 25;267(3):1719–1726. [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