Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 Jul;84(1):107–112. doi: 10.1172/JCI114129

Complement-mediated phagocytosis of herpes simplex virus by granulocytes. Binding or ingestion.

J A Van Strijp 1, K P Van Kessel 1, M E van der Tol 1, J Verhoef 1
PMCID: PMC303959  PMID: 2544621

Abstract

The role of complement receptors in phagocytosis of herpes simplex virus (HSV) by PMN was examined. Complement components were deposited on the surface of the virus particle in the presence or absence of specific anti-HSV antibodies. Flow cytometry was used to analyze the phagocytosis of fluorescence-labeled viruses and demonstrated that although a virion is able to associate with PMN in the presence of complement alone, the granulocyte is not triggered to mount a metabolic burst. Efficient stimulation of PMN occurs when complexes are formed consisting of virus, specific antibodies, and complement. To address the question whether the viruses were inside or outside the cell, a combined enhancement/quenching method was developed using ammonium chloride as a lysosomotropic agent and trypan blue as a quenching dye. The data indicate that Fc receptor-mediated phagocytosis by PMN results in the ingestion of all cell-associated herpes virions. Interactions of virions through PMN-complement receptors CR1 and CR3 results solely in binding to the PMN but not in internalization. Interactions via both complement and Fc receptors cause synergistic stimulation of the PMN and result in very efficient association of viruses, greater than 80% of which were inside the cell.

Full text

PDF
107

Selected References

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

  1. Aguado M. T., Lambris J. D., Tsokos G. C., Burger R., Bitter-Suermann D., Tamerius J. D., Dixon F. J., Theofilopoulos A. N. Monoclonal antibodies against complement 3 neoantigens for detection of immune complexes and complement activation. Relationship between immune complex levels, state of C3, and numbers of receptors for C3b. J Clin Invest. 1985 Oct;76(4):1418–1426. doi: 10.1172/JCI112119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bingham E. L., Fenger T. W., Sugar A., Smith J. W. Dependence on antibody for induction of chemiluminescence in polymorphonuclear leukocytes by herpes simplex virus. Invest Ophthalmol Vis Sci. 1985 Sep;26(9):1236–1243. [PubMed] [Google Scholar]
  3. Brown E. J. The role of extracellular matrix proteins in the control of phagocytosis. J Leukoc Biol. 1986 May;39(5):579–591. doi: 10.1002/jlb.39.5.579. [DOI] [PubMed] [Google Scholar]
  4. Cain J. A., Newman S. L., Ross G. D. Role of complement receptor type three and serum opsonins in the neutrophil response to yeast. Complement. 1987;4(2):75–86. doi: 10.1159/000463011. [DOI] [PubMed] [Google Scholar]
  5. Cassai E. N., Sarmiento M., Spear P. G. Comparison of the virion proteins specified by herpes simplex virus types 1 and 2. J Virol. 1975 Nov;16(5):1327–1331. doi: 10.1128/jvi.16.5.1327-1331.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cech P., Lehrer R. I. Phagolysosomal pH of human neutrophils. Blood. 1984 Jan;63(1):88–95. [PubMed] [Google Scholar]
  7. Changelian P. S., Fearon D. T. Tissue-specific phosphorylation of complement receptors CR1 and CR2. J Exp Med. 1986 Jan 1;163(1):101–115. doi: 10.1084/jem.163.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fearon D. T., Collins L. A. Increased expression of C3b receptors on polymorphonuclear leukocytes induced by chemotactic factors and by purification procedures. J Immunol. 1983 Jan;130(1):370–375. [PubMed] [Google Scholar]
  9. Fearon D. T., Kaneko I., Thomson G. G. Membrane distribution and adsorptive endocytosis by C3b receptors on human polymorphonuclear leukocytes. J Exp Med. 1981 Jun 1;153(6):1615–1628. doi: 10.1084/jem.153.6.1615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fries L. F., Siwik S. A., Malbran A., Frank M. M. Phagocytosis of target particles bearing C3b-IgG covalent complexes by human monocytes and polymorphonuclear leucocytes. Immunology. 1987 Sep;62(1):45–51. [PMC free article] [PubMed] [Google Scholar]
  11. Fujisawa H., Tsuru S., Taniguchi M., Zinnaka Y., Nomoto K. Protective mechanisms against pulmonary infection with influenza virus. I. Relative contribution of polymorphonuclear leukocytes and of alveolar macrophages to protection during the early phase of intranasal infection. J Gen Virol. 1987 Feb;68(Pt 2):425–432. doi: 10.1099/0022-1317-68-2-425. [DOI] [PubMed] [Google Scholar]
  12. Gordon D. L., Rice J., Finlay-Jones J. J., McDonald P. J., Hostetter M. K. Analysis of C3 deposition and degradation on bacterial surfaces after opsonization. J Infect Dis. 1988 Apr;157(4):697–704. doi: 10.1093/infdis/157.4.697. [DOI] [PubMed] [Google Scholar]
  13. Griffin F. M., Jr, Mullinax P. J. Augmentation of macrophage complement receptor function in vitro. V. Studies on the mechanisms of ligation of macrophage Fc receptors required to trigger macrophages to signal T lymphocytes to elaborate the lymphokine that activates macrophage C3 receptors for phagocytosis. J Immunol. 1985 Jul;135(1):344–349. [PubMed] [Google Scholar]
  14. Horwitz M. A. The roles of the Fc and C3 receptors in the phagocytosis and killing of bacteria by human phagocytes. J Reticuloendothel Soc. 1980 Dec;28(Suppl):17s–26s. [PubMed] [Google Scholar]
  15. Hurst J. K., Albrich J. M., Green T. R., Rosen H., Klebanoff S. Myeloperoxidase-dependent fluorescein chlorination by stimulated neutrophils. J Biol Chem. 1984 Apr 25;259(8):4812–4821. [PubMed] [Google Scholar]
  16. Kapp A., Freudenberg M., Galanos C. Induction of human granulocyte chemiluminescence by bacterial lipopolysaccharides. Infect Immun. 1987 Mar;55(3):758–761. doi: 10.1128/iai.55.3.758-761.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Klebanoff S. J., Beatty P. G., Schreiber R. D., Ochs H. D., Waltersdorph A. M. Effect of antibodies directed against complement receptors on phagocytosis by polymorphonuclear leukocytes: use of iodination as a convenient measure of phagocytosis. J Immunol. 1985 Feb;134(2):1153–1159. [PubMed] [Google Scholar]
  18. Lightfoote M., Folks T. M., Redfield R., Gold J., Marti G. E., Kelly J., Sell K. W. Flow-cytometric detection of circulating immune complexes. J Immunol Methods. 1986 Dec 4;95(1):107–112. doi: 10.1016/0022-1759(86)90323-6. [DOI] [PubMed] [Google Scholar]
  19. Ma J. A., Chapman G. V., Chen S. L., Penny R., Breit S. N. Flow cytometry with crystal violet to detect intracytoplasmic fluorescence in viable human lymphocytes. Demonstration of antibody entering living cells. J Immunol Methods. 1987 Nov 23;104(1-2):195–200. doi: 10.1016/0022-1759(87)90504-7. [DOI] [PubMed] [Google Scholar]
  20. Mantovani B. Different roles of IgG and complement receptors in phagocytosis by polymorphonuclear leukocytes. J Immunol. 1975 Jul;115(1):15–17. [PubMed] [Google Scholar]
  21. McCullough K. C., Parkinson D., Crowther J. R. Opsonization-enhanced phagocytosis of foot-and-mouth disease virus. Immunology. 1988 Oct;65(2):187–191. [PMC free article] [PubMed] [Google Scholar]
  22. Mehta R. L., Takahashi H., Rudick R. A., Knutson D. W. Binding and catabolism of aggregated immunoglobulins containing C3b by U937 cells. J Immunol. 1986 Mar 1;136(5):1765–1771. [PubMed] [Google Scholar]
  23. Meyers-Elliott R. H., Chitjian P. A. Immunopathogenesis of corneal inflammation in herpes simplex virus stromal keratitis: role of the polymorphonuclear leukocyte. Invest Ophthalmol Vis Sci. 1981 Jun;20(6):784–798. [PubMed] [Google Scholar]
  24. Ogle J. D., Ogle C. K., Noel J. G., Hurtubise P., Alexander J. W. Studies on the binding of C3b-coated microspheres to human neutrophils. J Immunol Methods. 1985 Jan 21;76(1):47–62. doi: 10.1016/0022-1759(85)90480-6. [DOI] [PubMed] [Google Scholar]
  25. Ohkuma S., Poole B. Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3327–3331. doi: 10.1073/pnas.75.7.3327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Porteu F., Mir A., Halbwachs-Mecarelli L. Modulation of neutrophil expression of C3b receptors (CR1) by soluble monomeric human C3b. Eur J Immunol. 1987 May;17(5):629–635. doi: 10.1002/eji.1830170508. [DOI] [PubMed] [Google Scholar]
  27. Ross G. D., Medof M. E. Membrane complement receptors specific for bound fragments of C3. Adv Immunol. 1985;37:217–267. doi: 10.1016/s0065-2776(08)60341-7. [DOI] [PubMed] [Google Scholar]
  28. Sahlin S., Hed J., Rundquist I. Differentiation between attached and ingested immune complexes by a fluorescence quenching cytofluorometric assay. J Immunol Methods. 1983 May 27;60(1-2):115–124. doi: 10.1016/0022-1759(83)90340-x. [DOI] [PubMed] [Google Scholar]
  29. Smith J. W., Jachimowicz J. R., Bingham E. L. Binding and internalization of herpes simplex virus-antibody complexes by polymorphonuclear leukocytes. J Med Virol. 1986 Oct;20(2):151–163. doi: 10.1002/jmv.1890200207. [DOI] [PubMed] [Google Scholar]
  30. Stevens D. A., Ferrington R. A., Jordan G. W., Merigan T. C. Cellular events in zoster vesicles: relation to clinical course and immune parameters. J Infect Dis. 1975 May;131(5):509–515. doi: 10.1093/infdis/131.5.509. [DOI] [PubMed] [Google Scholar]
  31. Tsuru S., Fujisawa H., Taniguchi M., Zinnaka Y., Nomoto K. Mechanism of protection during the early phase of a generalized viral infection. II. Contribution of polymorphonuclear leukocytes to protection against intravenous infection with influenza virus. J Gen Virol. 1987 Feb;68(Pt 2):419–424. doi: 10.1099/0022-1317-68-2-419. [DOI] [PubMed] [Google Scholar]
  32. Van Strijp J. A., Van Kessel K. P., van der Tol M. E., Fluit A. C., Snippe H., Verhoef J. Phagocytosis of herpes simplex virus by human granulocytes and monocytes. Arch Virol. 1989;104(3-4):287–298. doi: 10.1007/BF01315550. [DOI] [PubMed] [Google Scholar]
  33. Weber L., Peterhans E. Stimulation of chemiluminescence in bovine polymorphonuclear leucocytes by virus-antibody complexes and by antibody-coated infected cells. Immunobiology. 1983 May;164(5):333–342. doi: 10.1016/S0171-2985(83)80029-1. [DOI] [PubMed] [Google Scholar]
  34. West B. C., Escheté M. L., Cox M. E., King J. W. Neutrophil uptake of vaccinia virus in vitro. J Infect Dis. 1987 Oct;156(4):597–606. doi: 10.1093/infdis/156.4.597. [DOI] [PubMed] [Google Scholar]
  35. Williams J. D., Topley N., Alobaidi H. M., Harber M. J. Activation of human polymorphonuclear leucocytes by particulate zymosan is related to both its major carbohydrate components: glucan and mannan. Immunology. 1986 May;58(1):117–124. [PMC free article] [PubMed] [Google Scholar]
  36. Wright S. D., Griffin F. M., Jr Activation of phagocytic cells' C3 receptors for phagocytosis. J Leukoc Biol. 1985 Aug;38(2):327–339. doi: 10.1002/jlb.38.2.327. [DOI] [PubMed] [Google Scholar]
  37. Yancey K. B., O'Shea J., Chused T., Brown E., Takahashi T., Frank M. M., Lawley T. J. Human C5a modulates monocyte Fc and C3 receptor expression. J Immunol. 1985 Jul;135(1):465–470. [PubMed] [Google Scholar]
  38. van Strijp J. A., van Kessel K. P., Miltenburg L. A., Fluit A. C., Verhoef J. Attachment of human polymorphonuclear leukocytes to herpes simplex virus-infected fibroblasts mediated by antibody-independent complement activation. J Virol. 1988 Mar;62(3):847–850. doi: 10.1128/jvi.62.3.847-850.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES