Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1984 Apr 1;98(4):1328–1341. doi: 10.1083/jcb.98.4.1328

Interferon suppresses pinocytosis but stimulates phagocytosis in mouse peritoneal macrophages: related changes in cytoskeletal organization

PMCID: PMC2113216  PMID: 6371020

Abstract

Treatment of thioglycolate-elicited macrophages with mouse beta- interferon markedly reduces pinocytosis of horseradish peroxidase and fluorescein isothiocyanate (FITC)-dextran but stimulates phagocytosis of IgG-coated sheep erythrocytes. Experiments with FITC-dextran have revealed that the overall decrease in pinocytosis is due to a nearly complete inhibition of pinocytosis in a large fraction of interferon- treated macrophages. In the remaining cells pinocytosis continues at a rate similar to that in untreated control cells. A considerable reduction in the number of cells pinocytosing FITC-dextran was observed within 12 h from the beginning of interferon treatment. Measurement of the overall level of pinocytic activity with horseradish peroxidase showed a progressive decline through 72 h of treatment. In the interferon-sensitive subpopulation, there were marked changes in cytoskeletal organization. Microtubules and 10-nm filaments were aggregated in the perinuclear region while most of the peripheral cytoplasm became devoid of these cytoskeletal structures as observed by fluorescence and electron microscopy. In addition, interferon treatment of macrophages appeared to disrupt the close topological association between bundles of 10-nm filaments and organelles such as mitochondria, lysosomes, and elements of the Golgi apparatus and endoplasmic reticulum. Such alterations in the distribution of microtubules and 10- nm filaments were not seen in the interferon-insensitive subpopulation. We have investigated the mechanism of the interferon-induced enhancement of phagocytic activity by binding IgG-coated sheep erythrocytes to mouse peritoneal macrophages at 4 degrees C and then initiating a synchronous round of ingestion by warming the cells to 37 degrees C. Thioglycolate-elicited macrophages that had been treated with mouse beta-interferon ingested IgG-coated erythrocytes faster and to a higher level than control cells in a single round of phagocytosis. In interferon-treated cultures, phagocytic cups became evident within 30 s of the shift of cultures from 4 degrees to 37 degrees C, whereas in control cultures, they appeared in 2 min. Cytochalasin D, an inhibitor of actin assembly and polymerization, abolished phagocytic activity in both control and beta-interferon-treated macrophages. However, to inhibit phagocytosis completely in thioglycolate-elicited interferon-treated macrophages, twice as much cytochalasin D was required in the treated as in control cultures.(ABSTRACT TRUNCATED AT 400 WORDS)

Full Text

The Full Text of this article is available as a PDF (1.7 MB).

Selected References

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

  1. Barak L. S., Yocum R. R., Nothnagel E. A., Webb W. W. Fluorescence staining of the actin cytoskeleton in living cells with 7-nitrobenz-2-oxa-1,3-diazole-phallacidin. Proc Natl Acad Sci U S A. 1980 Feb;77(2):980–984. doi: 10.1073/pnas.77.2.980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Begg D. A., Rodewald R., Rebhun L. I. The visualization of actin filament polarity in thin sections. Evidence for the uniform polarity of membrane-associated filaments. J Cell Biol. 1978 Dec;79(3):846–852. doi: 10.1083/jcb.79.3.846. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blalock J. E., Stanton J. D. Common pathways of interferon and hormonal action. Nature. 1980 Jan 24;283(5745):406–408. doi: 10.1038/283406a0. [DOI] [PubMed] [Google Scholar]
  4. Chandrabose K., Cuatrecasas P., Pottathil R. Changes in fatty acyl chains of phospholipids induced by interferon in mouse sarcoma S-180 cells. Biochem Biophys Res Commun. 1981 Feb 12;98(3):661–668. doi: 10.1016/0006-291x(81)91165-7. [DOI] [PubMed] [Google Scholar]
  5. Chang C. M., Goldman R. D. The localization of actin-like fibers in cultured neuroblastoma cells as revealed by heavy meromyosin binding. J Cell Biol. 1973 Jun;57(3):867–874. doi: 10.1083/jcb.57.3.867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chany C. Membrane-bound interferon specific cell receptor system: role in the establishment and amplification of the antiviral state. Biomedicine. 1976 Jun;24(3):148–157. [PubMed] [Google Scholar]
  7. Diamond B., Yelton D. E. A new Fc receptor on mouse macrophages binding IgG3. J Exp Med. 1981 Mar 1;153(3):514–519. doi: 10.1084/jem.153.3.514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Donahoe R. M., Huang K. Y. Interferon preparations enhance phagocytosis in vivo. Infect Immun. 1976 Apr;13(4):1250–1257. doi: 10.1128/iai.13.4.1250-1257.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Friedman R. M. Antiviral activity of interferons. Bacteriol Rev. 1977 Sep;41(3):543–567. doi: 10.1128/br.41.3.543-567.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Friedman R. M. Interferon binding: the first step in establishment of antiviral activity. Science. 1967 Jun 30;156(3783):1760–1761. doi: 10.1126/science.156.3783.1760. [DOI] [PubMed] [Google Scholar]
  11. Graham R. C., Jr, Karnovsky M. J. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. doi: 10.1177/14.4.291. [DOI] [PubMed] [Google Scholar]
  12. Gresser I., Bourali C. Antitumor effects of interferon preparations in mice. J Natl Cancer Inst. 1970 Aug;45(2):365–376. [PubMed] [Google Scholar]
  13. Gresser I. On the varied biologic effects of interferon. Cell Immunol. 1977 Dec;34(2):406–415. doi: 10.1016/0008-8749(77)90262-3. [DOI] [PubMed] [Google Scholar]
  14. Hamburg S. I., Fleit H. B., Unkeless J. C., Rabinovitch M. Mononuclear phagocytes: responders to and producers of interferon. Ann N Y Acad Sci. 1980;350:72–90. doi: 10.1111/j.1749-6632.1980.tb20609.x. [DOI] [PubMed] [Google Scholar]
  15. Hubbard A. L., Cohn Z. A. Externally disposed plasma membrane proteins. II. Metabolic fate of iodinated polypeptides of mouse L cells. J Cell Biol. 1975 Feb;64(2):461–479. doi: 10.1083/jcb.64.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. LUFT J. H. Improvements in epoxy resin embedding methods. J Biophys Biochem Cytol. 1961 Feb;9:409–414. doi: 10.1083/jcb.9.2.409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Locke M., Krishnan N. Hot alcoholic phosphotungstic acid and uranyl acetate as routine stains for thick and thin sections. J Cell Biol. 1971 Aug;50(2):550–557. doi: 10.1083/jcb.50.2.550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mahoney E. M., Hamill A. L., Scott W. A., Cohn Z. A. Response of endocytosis to altered fatty acyl composition of macrophage phospholipids. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4895–4899. doi: 10.1073/pnas.74.11.4895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mahoney E. M., Scott W. A., Landsberger F. R., Hamill A. L., Cohn Z. A. Influence of fatty acyl substitution on the composition and function of macrophage membranes. J Biol Chem. 1980 May 25;255(10):4910–4917. [PubMed] [Google Scholar]
  21. Michl J., Ohlbaum D. J., Silverstein S. C. 2-Deoxyglucose selectively inhibits Fc and complement receptor-mediated phagocytosis in mouse peritoneal macrophages. I. Description of the inhibitory effect. J Exp Med. 1976 Dec 1;144(6):1465–1483. doi: 10.1084/jem.144.6.1465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Michl J., Pieczonka M. M., Unkeless J. C., Silverstein S. C. Effects of immobilized immune complexes on Fc- and complement-receptor function in resident and thioglycollate-elicited mouse peritoneal macrophages. J Exp Med. 1979 Sep 19;150(3):607–621. doi: 10.1084/jem.150.3.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Michl J., Unkeless J. C., Pieczonka M. M., Silverstein S. C. Modulation of Fc receptors of mononuclear phagocytes by immobilized antigen-antibody complexes. Quantitative analysis of the relationship between ligand number and Fc receptor response. J Exp Med. 1983 Jun 1;157(6):1746–1757. doi: 10.1084/jem.157.6.1746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Muller W. A., Steinman R. M., Cohn Z. A. The membrane proteins of the vacuolar system. II. Bidirectional flow between secondary lysosomes and plasma membrane. J Cell Biol. 1980 Jul;86(1):304–314. doi: 10.1083/jcb.86.1.304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. PAUCKER K., CANTELL K., HENLE W. Quantitative studies on viral interference in suspended L cells. III. Effect of interfering viruses and interferon on the growth rate of cells. Virology. 1962 Jun;17:324–334. doi: 10.1016/0042-6822(62)90123-x. [DOI] [PubMed] [Google Scholar]
  26. Pfeffer L. M., Landsberger F. R., Tamm I. Beta-interferon-induced time-dependent changes in the plasma membrane lipid bilayer of cultured cells. J Interferon Res. 1981;1(4):613–620. doi: 10.1089/jir.1981.1.613. [DOI] [PubMed] [Google Scholar]
  27. Pfeffer L. M., Murphy J. S., Tamm I. Interferon effects on the growth and division of human fibroblasts. Exp Cell Res. 1979 Jun;121(1):111–120. doi: 10.1016/0014-4827(79)90450-6. [DOI] [PubMed] [Google Scholar]
  28. Pfeffer L. M., Tamm I. Effects of beta interferon on concanavalin A binding and size of HeLa cells. J Interferon Res. 1982;2(3):431–440. doi: 10.1089/jir.1982.2.431. [DOI] [PubMed] [Google Scholar]
  29. Pfeffer L. M., Wang E., Tamm I. Interferon effects on microfilament organization, cellular fibronectin distribution, and cell motility in human fibroblasts. J Cell Biol. 1980 Apr;85(1):9–17. doi: 10.1083/jcb.85.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pfeffer L. M., Wang E., Tamm I. Interferon inhibits the redistribution of cell surface components. J Exp Med. 1980 Aug 1;152(2):469–474. doi: 10.1084/jem.152.2.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Phaire-Washington L., Silverstein S. C., Wang E. Phorbol myristate acetate stimulates microtubule and 10-nm filament extension and lysosome redistribution in mouse macrophages. J Cell Biol. 1980 Aug;86(2):641–655. doi: 10.1083/jcb.86.2.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Phaire-Washington L., Wang E., Silverstein S. C. Phorbol myristate acetate stimulates pinocytosis and membrane spreading in mouse peritoneal macrophages. J Cell Biol. 1980 Aug;86(2):634–640. doi: 10.1083/jcb.86.2.634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Pollard T. D., Shelton E., Weihing R. R., Korn E. D. Ultrastructural characterization of F-actin isolated from Acanthamoeba castellanii and identification of cytoplasmic filaments as F-actin by reaction with rabbit heavy meromyosin. J Mol Biol. 1970 May 28;50(1):91–97. doi: 10.1016/0022-2836(70)90106-3. [DOI] [PubMed] [Google Scholar]
  34. REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. SZENT-GYORGYI A. G. Meromyosins, the subunits of myosin. Arch Biochem Biophys. 1953 Feb;42(2):305–320. doi: 10.1016/0003-9861(53)90360-9. [DOI] [PubMed] [Google Scholar]
  36. Salisbury J. L., Condeelis J. S., Maihle N. J., Satir P. Receptor-mediated endocytosis by clathrin-coated vesicles: evidence for a dynamic pathway. Cold Spring Harb Symp Quant Biol. 1982;46(Pt 2):733–741. doi: 10.1101/sqb.1982.046.01.070. [DOI] [PubMed] [Google Scholar]
  37. Salisbury J. L., Condeelis J. S., Satir P. Role of coated vesicles, microfilaments, and calmodulin in receptor-mediated endocytosis by cultured B lymphoblastoid cells. J Cell Biol. 1980 Oct;87(1):132–141. doi: 10.1083/jcb.87.1.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Steinman R. M., Cohn Z. A. The interaction of soluble horseradish peroxidase with mouse peritoneal macrophages in vitro. J Cell Biol. 1972 Oct;55(1):186–204. doi: 10.1083/jcb.55.1.186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Unkeless J. C. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J Exp Med. 1979 Sep 19;150(3):580–596. doi: 10.1084/jem.150.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Unkeless J. C. The presence of two Fc receptors on mouse macrophages: evidence from a variant cell line and differential trypsin sensitivity. J Exp Med. 1977 Apr 1;145(4):931–945. doi: 10.1084/jem.145.4.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Valerius N. H., Stendahl O., Hartwig J. H., Stossel T. P. Distribution of actin-binding protein and myosin in polymorphonuclear leukocytes during locomotion and phagocytosis. Cell. 1981 Apr;24(1):195–202. doi: 10.1016/0092-8674(81)90515-8. [DOI] [PubMed] [Google Scholar]
  42. Vogel S. N., Finbloom D. S., English K. E., Rosenstreich D. L., Langreth S. G. Interferon-induced enhancement of macrophage Fc receptor expression: beta-interferon treatment of C3H/HeJ macrophages results in increased numbers and density of Fc receptors. J Immunol. 1983 Mar;130(3):1210–1214. [PubMed] [Google Scholar]
  43. Walter R. J., Berlin R. D., Pfeiffer J. R., Oliver J. M. Polarization of endocytosis and receptor topography on cultured macrophages. J Cell Biol. 1980 Jul;86(1):199–211. doi: 10.1083/jcb.86.1.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wang E., Choppin P. W. Effect of vanadate on intracellular distribution and function of 10-nm filaments. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2363–2367. doi: 10.1073/pnas.78.4.2363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wang E., Cross R. K., Choppin P. W. Involvement of microtubules and 10-nm filaments in the movement and positioning of nuclei in syncytia. J Cell Biol. 1979 Nov;83(2 Pt 1):320–337. doi: 10.1083/jcb.83.2.320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wang E., Goldman R. D. Functions of cytoplasmic fibers in intracellular movements in BHK-21 cells. J Cell Biol. 1978 Dec;79(3):708–726. doi: 10.1083/jcb.79.3.708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Wang E., Pfeffer L. M., Tamm I. Interferon increases the abundance of submembranous microfilaments in HeLa-S3 cells in suspension culture. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6281–6285. doi: 10.1073/pnas.78.10.6281. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES