Skip to main content
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
. 1996 Oct 29;93(22):12456–12460. doi: 10.1073/pnas.93.22.12456

Role for the class A macrophage scavenger receptor in the phagocytosis of apoptotic thymocytes in vitro.

N Platt 1, H Suzuki 1, Y Kurihara 1, T Kodama 1, S Gordon 1
PMCID: PMC38013  PMID: 8901603

Abstract

Numerous immature thymocytes undergo apoptosis and are rapidly engulfed by phagocytic thymic macrophages. The macrophage surface receptors involved in apoptotic thymocyte recognition are unknown. We have examined the role of the class A macrophage scavenger receptor (SR-A) in the engulfment of apoptotic thymocytes. Uptake of steroid-treated apoptotic thymocytes by thymic and inflammatory-elicited SR-A positive macrophages is partially inhibited by an anti-SR-A mAb and more completely by a range of scavenger receptor ligands. Thymic macrophages from mice with targeted disruption of the SR-A gene show a 50% reduction in phagocytosis of apoptotic thymocytes in vitro. These data suggest that SR-A may play a role in the clearance of dying cells in the thymus.

Full text

PDF
12456

Images in this article

Selected References

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

  1. Austyn J. M., Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol. 1981 Oct;11(10):805–815. doi: 10.1002/eji.1830111013. [DOI] [PubMed] [Google Scholar]
  2. Crocker P. R., Kelm S., Dubois C., Martin B., McWilliam A. S., Shotton D. M., Paulson J. C., Gordon S. Purification and properties of sialoadhesin, a sialic acid-binding receptor of murine tissue macrophages. EMBO J. 1991 Jul;10(7):1661–1669. doi: 10.1002/j.1460-2075.1991.tb07689.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Duijvestijn A. M., Hoefsmit E. C. Ultrastructure of the rat thymus: the micro-environment of T-lymphocyte maturation. Cell Tissue Res. 1981;218(2):279–292. doi: 10.1007/BF00210344. [DOI] [PubMed] [Google Scholar]
  4. Duvall E., Wyllie A. H., Morris R. G. Macrophage recognition of cells undergoing programmed cell death (apoptosis). Immunology. 1985 Oct;56(2):351–358. [PMC free article] [PubMed] [Google Scholar]
  5. Egerton M., Scollay R., Shortman K. Kinetics of mature T-cell development in the thymus. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2579–2582. doi: 10.1073/pnas.87.7.2579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Endemann G., Stanton L. W., Madden K. S., Bryant C. M., White R. T., Protter A. A. CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem. 1993 Jun 5;268(16):11811–11816. [PubMed] [Google Scholar]
  7. Fadok V. A., Savill J. S., Haslett C., Bratton D. L., Doherty D. E., Campbell P. A., Henson P. M. Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells. J Immunol. 1992 Dec 15;149(12):4029–4035. [PubMed] [Google Scholar]
  8. Fraser I., Hughes D., Gordon S. Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor. Nature. 1993 Jul 22;364(6435):343–346. doi: 10.1038/364343a0. [DOI] [PubMed] [Google Scholar]
  9. Hale G., Cobbold S. P., Waldmann H., Easter G., Matejtschuk P., Coombs R. R. Isolation of low-frequency class-switch variants from rat hybrid myelomas. J Immunol Methods. 1987 Oct 23;103(1):59–67. doi: 10.1016/0022-1759(87)90242-0. [DOI] [PubMed] [Google Scholar]
  10. Holness C. L., da Silva R. P., Fawcett J., Gordon S., Simmons D. L. Macrosialin, a mouse macrophage-restricted glycoprotein, is a member of the lamp/lgp family. J Biol Chem. 1993 May 5;268(13):9661–9666. [PubMed] [Google Scholar]
  11. Hughes D. A., Fraser I. P., Gordon S. Murine macrophage scavenger receptor: in vivo expression and function as receptor for macrophage adhesion in lymphoid and non-lymphoid organs. Eur J Immunol. 1995 Feb;25(2):466–473. doi: 10.1002/eji.1830250224. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Krieger M., Herz J. Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP). Annu Rev Biochem. 1994;63:601–637. doi: 10.1146/annurev.bi.63.070194.003125. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Kurihara Y., Kurihara H., Suzuki H., Kodama T., Maemura K., Nagai R., Oda H., Kuwaki T., Cao W. H., Kamada N. Elevated blood pressure and craniofacial abnormalities in mice deficient in endothelin-1. Nature. 1994 Apr 21;368(6473):703–710. doi: 10.1038/368703a0. [DOI] [PubMed] [Google Scholar]
  16. Kyewski B. A., Rouse R. V., Kaplan H. S. Thymocyte rosettes: multicellular complexes of lymphocytes and bone marrow-derived stromal cells in the mouse thymus. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5646–5650. doi: 10.1073/pnas.79.18.5646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lyons A. B., Samuel K., Sanderson A., Maddy A. H. Simultaneous analysis of immunophenotype and apoptosis of murine thymocytes by single laser flow cytometry. Cytometry. 1992;13(8):809–821. doi: 10.1002/cyto.990130803. [DOI] [PubMed] [Google Scholar]
  18. McPhee D., Pye J., Shortman K. The differentiation of T lymphocytes. V. Evidence for intrathymic death of most thymocytes. Thymus. 1979 Nov;1(3):151–162. [PubMed] [Google Scholar]
  19. Ottnad E., Parthasarathy S., Sambrano G. R., Ramprasad M. P., Quehenberger O., Kondratenko N., Green S., Steinberg D. A macrophage receptor for oxidized low density lipoprotein distinct from the receptor for acetyl low density lipoprotein: partial purification and role in recognition of oxidatively damaged cells. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1391–1395. doi: 10.1073/pnas.92.5.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pearson A., Lux A., Krieger M. Expression cloning of dSR-CI, a class C macrophage-specific scavenger receptor from Drosophila melanogaster. Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):4056–4060. doi: 10.1073/pnas.92.9.4056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Raff M. C. Social controls on cell survival and cell death. Nature. 1992 Apr 2;356(6368):397–400. doi: 10.1038/356397a0. [DOI] [PubMed] [Google Scholar]
  22. Ren Y., Silverstein R. L., Allen J., Savill J. CD36 gene transfer confers capacity for phagocytosis of cells undergoing apoptosis. J Exp Med. 1995 May 1;181(5):1857–1862. doi: 10.1084/jem.181.5.1857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rosen H., Gordon S. Monoclonal antibody to the murine type 3 complement receptor inhibits adhesion of myelomonocytic cells in vitro and inflammatory cell recruitment in vivo. J Exp Med. 1987 Dec 1;166(6):1685–1701. doi: 10.1084/jem.166.6.1685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sambrano G. R., Parthasarathy S., Steinberg D. Recognition of oxidatively damaged erythrocytes by a macrophage receptor with specificity for oxidized low density lipoprotein. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3265–3269. doi: 10.1073/pnas.91.8.3265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sambrano G. R., Steinberg D. Recognition of oxidatively damaged and apoptotic cells by an oxidized low density lipoprotein receptor on mouse peritoneal macrophages: role of membrane phosphatidylserine. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1396–1400. doi: 10.1073/pnas.92.5.1396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Savill J., Dransfield I., Hogg N., Haslett C. Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature. 1990 Jan 11;343(6254):170–173. doi: 10.1038/343170a0. [DOI] [PubMed] [Google Scholar]
  27. Savill J., Fadok V., Henson P., Haslett C. Phagocyte recognition of cells undergoing apoptosis. Immunol Today. 1993 Mar;14(3):131–136. doi: 10.1016/0167-5699(93)90215-7. [DOI] [PubMed] [Google Scholar]
  28. Surh C. D., Sprent J. T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature. 1994 Nov 3;372(6501):100–103. doi: 10.1038/372100a0. [DOI] [PubMed] [Google Scholar]
  29. Tepass U., Fessler L. I., Aziz A., Hartenstein V. Embryonic origin of hemocytes and their relationship to cell death in Drosophila. Development. 1994 Jul;120(7):1829–1837. doi: 10.1242/dev.120.7.1829. [DOI] [PubMed] [Google Scholar]
  30. Wyllie A. H., Kerr J. F., Currie A. R. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. doi: 10.1016/s0074-7696(08)62312-8. [DOI] [PubMed] [Google Scholar]
  31. el Khoury J., Thomas C. A., Loike J. D., Hickman S. E., Cao L., Silverstein S. C. Macrophages adhere to glucose-modified basement membrane collagen IV via their scavenger receptors. J Biol Chem. 1994 Apr 8;269(14):10197–10200. [PubMed] [Google Scholar]
  32. von Boehmer H. The developmental biology of T lymphocytes. Annu Rev Immunol. 1988;6:309–326. doi: 10.1146/annurev.iy.06.040188.001521. [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