Skip to main content

Advertisement

SpringerLink
Log in

Role of IgE Immune Complexes in the Regulation of HIV-1 Replication and Increased Cell Death of Infected U1 Monocytes: Involvement of CD23/FcεRII-Mediated Nitric Oxide and Cyclic AMP Pathways

  • Original Articles
  • Published:
Molecular Medicine Aims and scope Submit manuscript

Abstract

Background

IgE/anti-IgE immune complexes (IgE-IC) induce the release of multiple mediators from monocytes/macrophages and the monocytic cell line U937 following the ligation of the low-affinity Fcε receptors (FcεRII/CD23). These effects are mediated through an accumulation of cAMP and the generation of L-arginine-dependent nitric oxide (NO). Since high IgE levels predict more rapid progression to acquired immunodeficiency syndrome, we attempted to define the effects of IgE-IC on human immunodeficiency virus (HIV) production in monocytes.

Materials and Methods

Two variants of HIV-1 chronically infected monocytic U1 cells were stimulated with IgE-IC and virus replication was quantified. NO and cAMP involvement was tested through the use of agonistic and antagonistic chemicals of these two pathways.

Results

IgE-IC induced p24 production by U1 cells with low-level constitutive expression of HIV-1 mRNAs and extracellular HIV capsid protein p24 levels (U1low), upon their pretreatment with interleukin 4 (IL-4) or IL-13. This effect was due to the crosslinking of CD23, as it was reversed by blocking the IgE binding site on CD23. The IgE-IC effect could also be mimicked by crosslinking of CD23 by a specific monoclonal antibody. p24 induction by IgE-IC was then shown to be due to CD23-mediated stimulation of cAMP, NO, and tumor necrosis factor α (TNFα) generation. In another variant of U1 cells with >1 log higher constitutive production of p24 levels (U1high), IgE-IC addition dramatically decreased all cell functions tested and accelerated cell death. This phenomenon was reversed by blocking the nitric oxide generation.

Conclusions

These data point out a regulatory role of IgE-IC on HIV-1 production in monocytic cells, through CD23-mediated stimulation of cAMP and NO pathways. IgE-IC can also stimulate increased cell death in high HTV producing cells through the NO pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Gartner SP, Markovits DM, Kaplan MH, Gallo RC, Popovic M. (1986) The role of mononuclear phagocytes in HTLV-II/LAV infection. Science 233: 215–219.

    Article  CAS  Google Scholar 

  2. Gendelmen HE, Orentstein JM, Martin MA, et al. (1988) Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor-1 treated monocytes. J. Exp. Med. 167: 1428–1441.

    Article  Google Scholar 

  3. Schuitemaker H, Kootstra NA, DeGoede REY, Dewolf F, Miedema F, Tersmette M. (1991) Monocytotropic human immunodeficiency virus type 1 (HIV-1) variants detectable at all stages of HIV-1 infection lack T-cell tropism and syncytium-inducing ability in primary T-cell culture. J. Virol. 65: 356–363.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Stevenson M, Stanwick TL, Dempsey DP, Lamonica CA. (1990) HIV-1 replication is controlled at the level of T cell activation and proviral integration. EMBO J. 9: 1551–1560.

    Article  CAS  Google Scholar 

  5. Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, Chen ISY. (1990) HIV-1 entry into quiescent primary lymphocytes: Molecular analysis reveals a labile, latent viral structure. Cell 61: 213–222.

    Article  CAS  Google Scholar 

  6. Mikovits JA, Lohrey NC, Schulof R, Courtless J, Ruscetti FW. (1992) Activation of infectious virus from latent human immunodeficiency virus infection of monocytes in vivo. J. Clin. Invest. 90: 1486–1491.

    Article  CAS  Google Scholar 

  7. Embertson J, Zupancic M, Ribas JL, et al. (1993) Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature 362: 359–361.

    Article  Google Scholar 

  8. Mikovits JA, Raziuddin R, Ribas JL, et al. (1990) Negative regulation of human immune deficiency virus replication in monocytes. Distinctions between restricted and latent expression in THP-1 cells. J. Exp. Med. 171: 1705–1720.

    Article  CAS  Google Scholar 

  9. Folks TM, Justement J, Kinter A, et al. (1988) Characterization of promonocyte clone chronically infected with HIV and inducible by 13-phorbol-12-myristate acetate. J. Immunol. 140: 1117–1124.

    CAS  PubMed  Google Scholar 

  10. Pantaleo G, Graziosi C, Demarest JF, et al. (1993) HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature 362: 355–358.

    Article  CAS  Google Scholar 

  11. Ishizaka K. (1989) Basic mechanism of IgE-mediated hypersensitivity. Curr. Opin. Immunol. 4: 625–629.

    Google Scholar 

  12. Stevens RL, Austen F. (1989) Recent advances in the cellular and molecular biology of mast cells. Immunol. Today 10: 381–386.

    Article  CAS  Google Scholar 

  13. Galli SJ. (1991) New concepts about the mast cell. N. Engl. J. Med. 328: 257–265.

    Google Scholar 

  14. Borish L, Mascali JJ, Rosenwasser LJ. (1991) IgE-dependent cytokine production by human peripheral blood mononuclear phagocytes. J. Immunol. 146: 63–67.

    CAS  PubMed  Google Scholar 

  15. Capron M, Jouault T, Prin L, et al. (1986) Functional study of a monoclonal antibody to IgE Fc receptor (FcεR2) of eosinophils, platelets and macrophages. J. Exp. Med. 164: 72–89.

    Article  CAS  Google Scholar 

  16. Mossalayi MD, Paul-Eugène N, Ouaaz F, et al. (1994) Involvement of FcεRII/CD23 and L-arginine-dependent pathway in IgE-mediated stimulation of human monocyte functions. Int. Immunol. 6: 931–934.

    Article  CAS  Google Scholar 

  17. Israel-Biet D, Labrousse F, Tourani JM, Sors H, Andrieu JM, Even P. (1992) Elevation of IgE in HIV-infected subjects: A marker of poor prognosis. J. Allergy Clin. Immunol. 89: 68–75.

    Article  CAS  Google Scholar 

  18. Sample S, Chernoff DN, Lenahan GA, et al. (1990) Elevated serum concentrations of IgE antibodies to environmental antigens in HIV-seropositive male homosexuals. J. Allergy Clin. Immunol. 86: 876–880.

    Article  CAS  Google Scholar 

  19. Paganelli R, Scala E, Ansotegui IJ, et al. (1995) CD8+ T lymphocytes provide helper activity for IgE synthesis in human immunodeficiency virus-infected patients with hyper-IgE. J. Exp. Med. 181: 423–428.

    Article  CAS  Google Scholar 

  20. Unanue E, Allen PM. (1987) The basis for the immunoregulatory role of macrophages and other accessory cells. Science 236: 551–554.

    Article  CAS  Google Scholar 

  21. Maurer D, Fiebiger E, Reininger B, et al. (1994) Expression of functional high-affinity immunoglobulin E receptors (FcεRI) on monocytes of atopic individuals. J. Exp. Med. 179: 745–750.

    Article  CAS  Google Scholar 

  22. Delespesse G, Suter U, Mossalayi MD, et al. (1991) Expression, structure and functions of CD23 antigen. Adv. Immunol. 49: 149–191.

    Article  CAS  Google Scholar 

  23. Conrad DH. (1990) FcεRII/CD23: The low affinity receptor for IgE. Annu. Rev. Immunol. 8: 623–645.

    Article  CAS  Google Scholar 

  24. Ouaaz F, Sola B, Issaly F, et al. (1994) Growth arrest and terminal differentiation of leukemic myelomonocytic cells induced through the ligation of CD23 antigen. Blood 84: 3095–3104.

    CAS  PubMed  Google Scholar 

  25. Paul Eugène N, Kolb JP, Sarfati M, et al. (1995) Ligation of CD23 activates soluble guanylate cyclase in human monocytes via an L-arginine-dependent mechanism. J. Leuk. Biol. 57: 160–167.

    Article  Google Scholar 

  26. Mossalayi MD, Arock M, Delespesse G, et al. (1992) Cytokine effects of CD23 are mediated by an epitope distinct from the IgE binding site. EMBO J. 11: 3423–4328.

    Article  Google Scholar 

  27. Bécherel PA, Mossalayi MD, Dugas B, et al. (1994) Involvement of the cAMP and nitric oxide pathway in the IgE-dependent activation of normal human keratinocytes. J. Clin. Invest. 93: 2275–2279.

    Article  Google Scholar 

  28. Wang B, Rieger A, Kilgus O, et al. (1992) Epidermal Langerhans cells from normal human skin bind monomeric IgE via FcεRI. J. Exp. Med. 175: 1353–1365.

    Article  CAS  Google Scholar 

  29. Montaner LJ, Gordon S. (1995) TH2 down-regulation of macrophage HIV-1 replication. Science 267: 538–539.

    Article  CAS  Google Scholar 

  30. Kolb JP, Paul-Eugène N, Abadie A, Yamaoka K, Drapier JC, Dugas B. (1994) IL-4 stimulates cGMP production by IFN-γ-activated human monocytes. Involvement of the nitric oxide synthase pathway. J. Biol. Chem. 269: 9811–9816.

    CAS  PubMed  Google Scholar 

  31. Byrne B, Li J, Sninsky J, Poiesz BJ. (1988) Detection of HIV RNA sequences by in vitro DNA amplifications. Nucleic Acid. Res. 16: 4165–4168.

    Article  CAS  Google Scholar 

  32. Poiesz BJ, Ehrlich GD, Byrne BC, Wells K, Kwok S, Sninsky J. 1990. The use of polymerase chain reaction in the detection, quantification, and characterization of human retroviruses. In: de la Maza LM, Peterson EM (eds). Medical Virology. Plenum Press, New York, pp. 47–72.

    Google Scholar 

  33. Kwok S, Ehrich G, Poiesz B, Kalish R, Sninsky J. (1988) Enzymatic amplification of HTLV-1 viral sequences from peripheral blood mononuclear cells and infected tissues. Blood 72: 1117–1126.

    CAS  PubMed  Google Scholar 

  34. Gendelman H, Friedman R, Joe S, et al. (1990) A selective defect of interferon-alpha production in human immuno-deficiency virus-infected monocytes. J. Exp. Med. 172: 1433–1442.

    Article  CAS  Google Scholar 

  35. Vercelli D, Jabara HH, Lee BW, Woodland N, Geha RS, Leung DY. (1988) Human recombinant interleukin 4 induces FcεRII/CD23 on normal human monocytes. J. Exp. Med. 167: 1406–1416.

    Article  CAS  Google Scholar 

  36. Takizawa F, Adamczewski M, Kinet JP. (1992) Identification of the low affinity receptor for immunoglobulin E on mouse mast cells and macrophages as FcγRII and FcγRIII. J. Exp. Med. 176: 469–476.

    Article  CAS  Google Scholar 

  37. Figeri LG, Liu FT. (1992) Surface expression of functional IgE binding protein, and an endogenous lectin, on mast cells and macrophages. J. Immunol. 148: 961–967.

    Google Scholar 

  38. Paul-Eugène N, Kolb JP, Abadie A, et al. (1992) Ligation of CD23 triggers cAMP generation and release of inflammatory mediators in human monocytes. J. Immunol. 149: 3066–3071.

    PubMed  Google Scholar 

  39. Zuckerman KS, De Vries JE. (1994) Interleukin-13, an IL-4 like cytokine that acts on monocytes and B cells but not on T cells. Immunol. Today 15: 19–26.

    Article  Google Scholar 

  40. Feelisch M. (1991) The biochemical pathways of nitric oxide formation from nitrovasodilators: Appropriate choice of exogenous NO donors and aspects of preparation and handling of aqueous NO solutions. J. Cardio-vasc. Pharmacol. 17(Suppl 3): S25–S33.

    Article  CAS  Google Scholar 

  41. Nussler AK, Billiar TR. (1993) Inflammation, immunoregulation and inducible nitric oxide synthase. J. Leuk. Biol. 54: 171–178.

    Article  CAS  Google Scholar 

  42. Moneada S, Higgs A. (1993) The L-arginine nitric oxide pathway. N. Engl. J. Med. 30: 2002–2012.

    Google Scholar 

  43. Stuehr DJ, Griffith OW. (1992) Mammalian nitric oxide synthases. Adv. Enzymol. 65: 287–346.

    CAS  PubMed  Google Scholar 

  44. Duvall E, Wyllie AH. (1986) Death and the cell. Immunol. Today 7: 115–119.

    Article  CAS  Google Scholar 

  45. Albina JE, Cui S, Mateo RB, Reichner JS. (1993) Nitric oxide-mediated apoptosis in murine peritoneal macrophages. J. Immunol 150: 5080–5085.

    CAS  PubMed  Google Scholar 

  46. Mossalayi MD, Arock M, Bertho JM, et al. (1990) Proliferation of early human myeloid precursors induced by interleukin-1 and recombinant soluble CD23. Blood 75: 1924–1927.

    CAS  PubMed  Google Scholar 

  47. Gordon J. (1991) CD23: A novel multifunctional regulator of the immune system that bind IgE. In: Hanson LA, Shakib F (eds). Monographs in Allergy. Karger, Basel, pp. 1–208.

    Google Scholar 

  48. Aubry JP, Pochon S, Graber P, Jansen KU, Bonnefoy JY. (1992) CD21 is a ligand for CD23 and regulates IgE production. Nature 358: 505–508.

    Article  CAS  Google Scholar 

  49. Arock M, Le Goff L, Bécherel PA, Dugas B, Debré P, Mossalayi MD. (1994) Involvement of FcεRII/CD23 and L-arginine dependent pathway in IgE mediated activation of human eosinophils. Biochem. Biophys. Res. Commun. 203: 265–271.

    Article  CAS  Google Scholar 

  50. De Maria R, Cifone MG, Trotta R, et al. (1994) Triggering of human monocyte activation through CD69, a member of the natural killer gene complex family of signal transducing receptors. J. Exp. Med. 180: 1999–2004.

    Article  Google Scholar 

  51. Cifone MG, Festuccia C, Cironi L, et al. (1994) Induction of nitric oxide-synthesizing pathway in fresh and interleukin 2-cultured rat natural killer cells. Cell. Immunol. 157: 181–194.

    Article  CAS  Google Scholar 

  52. Chowdhury MI, Koyonagi Y, Horiuchi S, et al. (1993) cAMP stimulates human immunodeficiency virus (HIV-1) from latently infected cells of monocyte-macrophage lineage: Synergism with TNF-α. Virology 194: 345–349.

    Article  CAS  Google Scholar 

  53. Hassan MI, Nokta MA, Pollard RB. (1993) Involvement of cAMP and protein kinase C in cytomegalovirus enhancement of human immunodeficiency virus replication. Proc. Soc. Exp. Biol. Med. 204: 216–223.

    Article  CAS  Google Scholar 

  54. Hofmenn B, Nishanian P, Nguyen T, Liu M, Fahey JL. (1993) Restoration of T-cell function in HIV infection by reduction of intracellular cAMP levels with adenosine analogues. AIDS 7: 659–664.

    Article  Google Scholar 

  55. Karupiah G, Xie QW, Buller R, Nathan C, Duarte C, MacMicking JD. (1993) Inhibition of viral replication by interferon-γ-induced nitric oxide synthase. Science 261: 1445–1448.

    Article  CAS  Google Scholar 

  56. Croen KD. (1993) Evidence for an antiviral effect of nitric oxide. Inhibition of herpes simplex virus type 1 replication. J. Clin. Invest. 91: 2446–2452.

    Article  CAS  Google Scholar 

  57. Mannick JB, Asano K, Izumi K, Kleff E, Stamler JS. (1994) Nitric oxide produced by human B lymphocytes inhibits apoptosis and Epstein-Barr virus reactivation. Cell 79: 1137–1146.

    Article  CAS  Google Scholar 

  58. Schreck R, Rieber P, Bauerle PA. (1991) Reactive oxygen intermediates as apparently widely used messengers in the activation of NF-κB transcription factor and HIV-1. EMBO J. 10: 2247–2258.

    Article  CAS  Google Scholar 

  59. Chartrain NA, Geller DA, Koty PP, et al. (1994) Molecular cloning, structure, and chromosomal localization of the human inducible nitric oxide synthase gene. J. Biol. Chem. 269: 6765–6772.

    CAS  PubMed  Google Scholar 

  60. Xie Q-W, Whisnant R, Nathan C. (1993) Promotor of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon y and bacterial lipopolysaccharide. J. Exp. Med. 177: 1779–1784.

    Article  CAS  Google Scholar 

  61. Hamid A, Springall DR, Riveros-Moreno V, et al. (1993) Induction of nitric oxide synthase in asthma. Lancet 342: 1510–1513.

    Article  CAS  Google Scholar 

  62. Pietraforte D, Tritarelli E, Testa U, Minetti M. (1994) gp120 HIV envelope glycoprotein increases the production of nitric oxide in human monocyte-derived macrophages. J. Leuk. Biol. 55: 175–182.

    Article  CAS  Google Scholar 

  63. Bukrinsky MI, Nottet HS, Schmidtmayerova H, et al. (1995) Regulation of nitric oxide synthase activity in human immunodeficiency virus type 1 (HIV-1)-infected monocytes: Implications for HIV-associated neurological disease. J. Exp. Med. 181: 735–745.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank N. Paul-Eugène, J. P. Kolb, J. Wietzerbin, and H. Valentin for their suggestions; F. Issaly for technical assistance; J. Banchereau for rIL-4 and rIL-13 gift; and M. Benhamou and M. Arock for reviewing our work. The contents of this publication do not necessarily reflect the views nor policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Author information

Authors and Affiliations

  1. Groupe d’Immuno-hématologie Moléculaire, CNRS URA625, Hôpital de la Pitié-Salpêtrière, 91 Bd de l’Hôpital, 75013, Paris, France

    Fateh Ouaaz, Bernard Dugas, Patrice Debr & M. Djavad Mossalayi

  2. Laboratory of Leukocyte Biology, Program Resources/DynCorp, Incorporated, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland, USA

    Francis W. Ruscetti

  3. Biological Carcinogenesis and Development Program, Program Resources/DynCorp, Incorporated, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland, USA

    Judy Mikovits

  4. Virology Department, CNRS EP57, Pitié-Salpêtrière Hospital, Paris, France

    Henri Agut

Authors
  1. Fateh Ouaaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francis W. Ruscetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernard Dugas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Judy Mikovits
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Henri Agut
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Patrice Debr
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Djavad Mossalayi
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Contributed by S. Moncada on August 30, 1995.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ouaaz, F., Ruscetti, F.W., Dugas, B. et al. Role of IgE Immune Complexes in the Regulation of HIV-1 Replication and Increased Cell Death of Infected U1 Monocytes: Involvement of CD23/FcεRII-Mediated Nitric Oxide and Cyclic AMP Pathways. Mol Med 2, 38–49 (1996). https://doi.org/10.1007/BF03402201

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03402201

Search

Navigation