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Increased monocyte-dependent suppression of polyclonal activation of B lymphocytes from cystinotic children

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Abstract

In infantile cystinosis the amino acid cystine preferentially accumulates in phagocytic cells, polymorphonuclear leucocytes (PMN) and monocytes, rather than in lymphocytes. We previously described functional abnormalities in the oxidative metabolism and locomotion of cystinotic PMN and monocytes. The present study shows an abnormal lymphocyte polyclonal activation as evidenced by a decreased immunoglobulin (Ig) production and generation of Ig-containing cells (ICC) in cultures of peripheral blood mononuclear cells (PBMC) from cystinotic children upon stimultion with pokeweed mitogen andStaphylococcus aureus Cowan I. However, monocyte depletion from cystinotic PBMC fully reconstituted Ig production and ICC generation, indicating: (1) the presence of an increased monocyte-dependent suppression on lymphocyte polyclonal activation, and (2) that the intrinsic ability of cystinotic lymphocytes to respond to polyclonal stimulation was preserved. The increased cystinotic monocytedependent suppressive effect was not mediated by prostaglandin E2 (PGE2) since its production by cystinotic PBMC upon polyclonal activation was not different from that of controls. In addition, the sensitivity of cystinotic lymphocytes to the immunosuppressive effect of varying concentrations of exogenous PGE2 was similar to that of controls. Finally, indomethacin and 2-mercaptoethanol, two agents able to scavenge hydroxyl (OH) radicals, restored Ig production by cystinotic PBMC, suggesting a role for reactive oxygen species in the increased cystinotic monocyte-dependent suppression.

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References

  1. Schneider JA, Schulman JD (1986) Cystinosis and the Fanconi syndrome. In: Andreoli TE, Hoffman JF, Fanestil DD, Schultz SG (eds) Physiology of membrane disorders. Plenum, New York, pp 985–997

    Google Scholar 

  2. Broyer M, Guillot M, Gubler MC, Habib R (1981) Infantile cystinosis: a reappraisal of early and late symptoms. In: Hamburger J, Crosnier J, Grunfeld JP, Maxwell MH (eds) Advances in nephrology, vol 10. Year Book Medical, Chicago, pp 137–166

    Google Scholar 

  3. Schulman JD, Wong VG, Kuwabara T, Bradley KH, Seegmiller JE (1970) Intracellular cystine content of leukocyte populations in cystinosis. Arch Intern Med 125: 660–664

    Google Scholar 

  4. Pintos-Morell G, Niaudet P, Jean G, Descamps-Latscha B (1985) Altered oxidative metabolism, motility and adherence in phagocytic cells from cystinotic children. Pediatr Res 19: 1318–1321

    Google Scholar 

  5. Broyer M, Donckerwolcke RA, Brunner FP, Brynger H, Jacobs C, Kramer P, Selwood NH, Wing AJ, Blake PH (1981) Combined report on regular dialysis and transplantation of children in Europe. Proc Eur Dial Transplant Assoc 18: 59–90

    Google Scholar 

  6. Pintos-Morell G, Niaudet P, Jean G, Descamps-Latscha B (1986) In vitro abnormal leucocyte functions in infantile cystinosis. Helv Paediatr Acta 41: 117A

    Google Scholar 

  7. Smolin LA, Schneider JA (1988) Measurement of total plasma cysteamine using high-performance liquid chromatography with electrochemical detection. Anal Biochem 168: 374–379

    Google Scholar 

  8. Horwitz DA, Allison AC, Ward P, Kight N (1977) Identification of human mononuclear leukocyte populations by esterase staining. Clin Exp Immunol 30: 289–298

    Google Scholar 

  9. Durandy A, Fischer A, Griscelli C (1979) Active suppression of B lymphocyte maturation by two different newborn T lymphocyte subsets. J Immunol 123: 2644–2650

    Google Scholar 

  10. Dray F, Charbonnel B, Maclouf J (1975) Radioimmunoassay of prostaglandins Fα, E1, and E2 in human plasma. Eur J Clin Invest 5: 311–318

    Google Scholar 

  11. Rosenberg SA, Lipsky PE (1979) Monocyte dependence of pokeweed mitogen-induced differentiation of immunoglobulin secreting cells from human peripheral blood mononuclear cells. J Immunol 122: 926–931

    Google Scholar 

  12. Rosenberg SA, Lipsky PE (1981) The role of monocytes in pokeweed mitogen-stimulated human B cell activation: separate requirements for intact monocytes and a soluble monocyte factor. J Immunol 126: 1341–1345

    Google Scholar 

  13. Thompson PA, Jelinek DF, Lipsky PE (1984) Regulation of human B cell proliferation by prostaglandin E2. J Immunol 133: 2446–2453

    Google Scholar 

  14. Jelinek DF, Thompson PA, Lipsky PE (1985) Regulation of human B cell activation by prostaglandin E2. Suppression of the generation of immunoglobulin-secreting cells. J Immunol 75: 1339–1349

    Google Scholar 

  15. Staite ND, Panayi GS (1982) Regulation of human immunoglobulin production in vitro by prostaglandin E2. Clin Exp Immunol 49: 115–122

    Google Scholar 

  16. Metzger Z, Hoffeld JT, Oppenheim JJ (1980) Macrophage-mediated suppression. I. Evidence for participation of both hydrogen peroxide and prostaglandins in suppression of murine lymphocyte proliferation. J Immunol 124: 983–988

    Google Scholar 

  17. Sagone AL Jr, Wells RM, De Mocko C (1980) Evidence that ·OH production by human PMNs is related to prostaglandin metabolism. Inflammation 4: 65–71

    Google Scholar 

  18. Hiller KO, Wilson RL (1983) Hydroxyl-free radicals and anti-inflammatory drugs: biological inactivation studies and reaction rate constants. Biochem Pharmacol 32: 2109–2111

    Google Scholar 

  19. Hoffeld JT (1981) Agents which block membrane lipid peroxidation enhance mouse spleen cell immune activities in vitro: relationship to the enhancing activity of 2-mercaptoethanol. Eur J Immunol 11: 371–376

    Google Scholar 

  20. Goodwin JS, Messner RP (1979) Sensitivity of lymphocytes to prostaglandin E2 increases in subjects over age 70. J Clin Invest 64: 434–439

    Google Scholar 

  21. Wakasugi N, Virelizier JL, Arenzana-Seisdedos F, Rothhut B, Mencia-Huerta JM, Russo-Marie F, Fiers W (1985) Defective IFN-γ production in the human neonate. II. Role of increased sensitivity to the suppresive effects of prostaglandin E. J Immunol 134: 172–176

    Google Scholar 

  22. Dore-Duffy P, Zurier RB (1981) Lymphocyte adherence in multiple sclerosis. Role of monocytes and increased sensitivity of MS lymphocytes to prostaglandin E1. Clin Immunol Immunopathol 19: 303–313

    Google Scholar 

  23. Hasler F, Bluestein HG, Zvaifler NJ, Epstein LB (1983) Analysis of the defects responsible for the impaired regulation of EBV-induced B cell proliferation by rheumatoid arthritis lymphocytes. II. Role of monocytes and the increased sensitivity of rheumatoid arthritis lymphocytes to prostaglandin E1. J Immunol 131: 768–772

    Google Scholar 

  24. Goldyne ME, Stobo JD (1979) Synthesis of prostaglandins by subpopulations of human peripheral blood monocytes. Prostaglandins 18: 687–693

    Google Scholar 

  25. Kennedy MS, Stobo JD, Goldyne ME (1980) In vitro synthesis of prostaglandins and related lipids by populations of human peripheral blood mononuclear cells. Prostaglandins 20: 135–145

    Google Scholar 

  26. Goodwin JS (1980) Modulation of concanavalin A-induced suppressor cell activation by prostaglandin E2. Cell Immunol 49: 421–425

    Google Scholar 

  27. Fischer A, Durandy A, Griscelli C (1981) Role of prostaglandin E2 in the induction of non specific T lymphocyte suppressor activity. J Immunol 126: 1452–1455

    Google Scholar 

  28. Zoschke DC, Messner RP (1984) Suppression of human lymphocyte mitogenesis mediated by phagocyte-released reactive oxygen species: comparative activities in normals and in chronic granulomatous disease. Clin Immunol Immunopathol 32: 29–40

    Google Scholar 

  29. Peterson PK, Sharp B, Gekken G, Brummitt C, Keane WF (1987) Opioid-mediated suppression of interferon-γ production by cultured peripheral blood mononuclear cells. J Clin Invest 80: 824–831

    Google Scholar 

  30. Greene AA, Marcusson EG, Pintos-Morell G, Schneider JA (1990) Characterization of the lysosomal cystine transport system in mouse L-929 fibroblasts. J Biol Chem 265: 9888–9895

    Google Scholar 

  31. Satomi S, Tanimura S, Kunori T, Taguchi Y, Kasai M (1983) Monitoring of B lymphocyte response with the protein-A plaque assay in kidney transplant patients. Transplantation 35: 324–328

    Google Scholar 

  32. Horsburhg T, Hall H, Wood RFM (1983) Spontaneous plaque-forming cells in renal transplant patients: possible correlation with antibody-mediated rejection. Transplantation 35: 511–513

    Google Scholar 

  33. McNaughton DC, White DJG (1985) Measurement of immune activity in transplant recipients. Transplant Proc 17: 669

    Google Scholar 

  34. Degiannis D, Tsakiris D, Briggs JD, Mowat AM, Junor BJR, Parrott DMV (1985) Comparison of protein A plaque assay in cyclosporine-and azathioprine-treated renal allograft recipients. Transplant Proc 17: 2593–2596

    Google Scholar 

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Authors and Affiliations

  1. Department of Paediatrics, Hospital “Germans Trías i Pujol”, Badalona, Spain

    Guillem Pintos-Morell

  2. INSERM Unit 192, Hôpital Necker-Enfants Malades, Paris, France

    Geneviève Jean & Patrick Niaudet

  3. Department of Physiology, Hôpital Necker-Enfants Malades, Paris, France

    Michèle Dechaux

Authors
  1. Guillem Pintos-Morell
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  2. Geneviève Jean
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  3. Michèle Dechaux
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  4. Patrick Niaudet
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Pintos-Morell, G., Jean, G., Dechaux, M. et al. Increased monocyte-dependent suppression of polyclonal activation of B lymphocytes from cystinotic children. Pediatr Nephrol 5, 597–602 (1991). https://doi.org/10.1007/BF00856649

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  • DOI: https://doi.org/10.1007/BF00856649

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