Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1996 Jun 1;183(6):2571–2579. doi: 10.1084/jem.183.6.2571

Enhancement of Antigen-specific functional responses by neutrophils from allergic patients

PMCID: PMC2192616  PMID: 8676078

Abstract

It has been demonstrated that neutrophils from healthy donors or from patients with inflammatory disorders can bind immunoglobulin (Ig) E proteins through binding to Mac-2/epsilon bp. Functional responses to allergens were assessed by measuring the respiratory burst and intracellular Ca2+ levels, and binding of allergens to neutrophils was assessed by flow cytometry analysis and fluorescence microscopy. In this article, we demonstrate that neutrophils sensitized to specific allergens (from allergic patients), but not from healthy donors, are sensitive to allergens of the same type as those that produce clinical allergic symptoms. The activation of neutrophils was analyzed by the induction of a respiratory burst that was detected with luminol- dependent chemiluminescence. Intracellular Ca2+ levels increased parallel to those of the inducing allergens. In addition, the specific binding of allergens on the cell surface was revealed by flow cytometry and allergen-FITC-labeled staining analyses. The present data suggest a restricted recognition of allergen by sensitive neutrophils, probably associated with the specific binding of the allergen to its corresponding IgE molecule, which is bound to the Mac-2/epsilon bp structure. These findings demonstrate a functional role of allergen- associated neutrophils during the allergic state.

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. Bieber T., de la Salle H., Wollenberg A., Hakimi J., Chizzonite R., Ring J., Hanau D., de la Salle C. Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI). J Exp Med. 1992 May 1;175(5):1285–1290. doi: 10.1084/jem.175.5.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bochner B. S., Undem B. J., Lichtenstein L. M. Immunological aspects of allergic asthma. Annu Rev Immunol. 1994;12:295–335. doi: 10.1146/annurev.iy.12.040194.001455. [DOI] [PubMed] [Google Scholar]
  3. Boulet L. P., Turcotte H., Boutet M., Montminy L., Laviolette M. Influence of natural antigenic exposure on expiratory flows, methacholine responsiveness, and airway inflammation in mild allergic asthma. J Allergy Clin Immunol. 1993 Apr;91(4):883–893. doi: 10.1016/0091-6749(93)90346-h. [DOI] [PubMed] [Google Scholar]
  4. Campbell A. M., Vignola A. M., Chanez P., Godard P., Bousquet J. Low-affinity receptor for IgE on human bronchial epithelial cells in asthma. Immunology. 1994 Aug;82(4):506–508. [PMC free article] [PubMed] [Google Scholar]
  5. Capron A., Dessaint J. P., Joseph M., Rousseaux R., Capron M., Bazin H. Interaction between IgE complexes and macrophages in the rat: a new mechanism of macrophage activation. Eur J Immunol. 1977 May;7(5):315–322. doi: 10.1002/eji.1830070515. [DOI] [PubMed] [Google Scholar]
  6. Carlson M., Håkansson L., Kämpe M., Stålenheim G., Peterson C., Venge P. Degranulation of eosinophils from pollen-atopic patients with asthma is increased during pollen season. J Allergy Clin Immunol. 1992 Jan;89(1 Pt 1):131–139. doi: 10.1016/s0091-6749(05)80050-8. [DOI] [PubMed] [Google Scholar]
  7. Cherayil B. J., Weiner S. J., Pillai S. The Mac-2 antigen is a galactose-specific lectin that binds IgE. J Exp Med. 1989 Dec 1;170(6):1959–1972. doi: 10.1084/jem.170.6.1959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edwards S. W. Cell signalling by integrins and immunoglobulin receptors in primed neutrophils. Trends Biochem Sci. 1995 Sep;20(9):362–367. doi: 10.1016/s0968-0004(00)89077-5. [DOI] [PubMed] [Google Scholar]
  9. Gagnon R., Akoum A., Hébert J. Lol p I-induced IL-4 and IFN-gamma production by peripheral blood mononuclear cells of atopic and nonatopic subjects during and out of the pollen season. J Allergy Clin Immunol. 1993 Apr;91(4):950–956. doi: 10.1016/0091-6749(93)90353-h. [DOI] [PubMed] [Google Scholar]
  10. Gounni A. S., Lamkhioued B., Ochiai K., Tanaka Y., Delaporte E., Capron A., Kinet J. P., Capron M. High-affinity IgE receptor on eosinophils is involved in defence against parasites. Nature. 1994 Jan 13;367(6459):183–186. doi: 10.1038/367183a0. [DOI] [PubMed] [Google Scholar]
  11. Grinstein S., Furuya W. Receptor-mediated activation of electropermeabilized neutrophils. Evidence for a Ca2+- and protein kinase C-independent signaling pathway. J Biol Chem. 1988 Feb 5;263(4):1779–1783. [PubMed] [Google Scholar]
  12. Hidalgo J., Muñiz M., Velasco A. Trimeric G proteins regulate the cytosol-induced redistribution of Golgi enzymes into the endoplasmic reticulum. J Cell Sci. 1995 Apr;108(Pt 4):1805–1815. doi: 10.1242/jcs.108.4.1805. [DOI] [PubMed] [Google Scholar]
  13. Ho M. K., Springer T. A. Mac-2, a novel 32,000 Mr mouse macrophage subpopulation-specific antigen defined by monoclonal antibodies. J Immunol. 1982 Mar;128(3):1221–1228. [PubMed] [Google Scholar]
  14. Hughes J. M., McKay K. O., Johnson P. R., Tragoulias S., Black J. L., Armour C. L. Neutrophil-induced human bronchial hyperresponsiveness in vitro--pharmacological modulation. Clin Exp Allergy. 1993 Apr;23(4):251–256. doi: 10.1111/j.1365-2222.1993.tb00318.x. [DOI] [PubMed] [Google Scholar]
  15. Lee T. H., Nagy L., Nagakura T., Walport M. J., Kay A. B. Identification and partial characterization of an exercise-induced neutrophil chemotactic factor in bronchial asthma. J Clin Invest. 1982 Apr;69(4):889–899. doi: 10.1172/JCI110528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Leffler H., Barondes S. H. Specificity of binding of three soluble rat lung lectins to substituted and unsubstituted mammalian beta-galactosides. J Biol Chem. 1986 Aug 5;261(22):10119–10126. [PubMed] [Google Scholar]
  17. Lew P. D., Wollheim C. B., Waldvogel F. A., Pozzan T. Modulation of cytosolic-free calcium transients by changes in intracellular calcium-buffering capacity: correlation with exocytosis and O2-production in human neutrophils. J Cell Biol. 1984 Oct;99(4 Pt 1):1212–1220. doi: 10.1083/jcb.99.4.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Liu F. T., Albrandt K., Mendel E., Kulczycki A., Jr, Orida N. K. Identification of an IgE-binding protein by molecular cloning. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4100–4104. doi: 10.1073/pnas.82.12.4100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Liu F. T. Molecular biology of IgE-binding protein, IgE-binding factors, and IgE receptors. Crit Rev Immunol. 1990;10(3):289–306. [PubMed] [Google Scholar]
  20. Liu F. T. S-type mammalian lectins in allergic inflammation. Immunol Today. 1993 Oct;14(10):486–490. doi: 10.1016/0167-5699(93)90263-K. [DOI] [PubMed] [Google Scholar]
  21. Martín F., Gualberto A., Sobrino F., Pintado E. Thimerosal induces calcium mobilization, fructose 2,6-bisphosphate synthesis and cytoplasmic alkalinization in rat thymus lymphocytes. Biochim Biophys Acta. 1991 Jan 10;1091(1):110–114. doi: 10.1016/0167-4889(91)90229-q. [DOI] [PubMed] [Google Scholar]
  22. Maurer D., Fiebiger E., Reininger B., Wolff-Winiski B., Jouvin M. H., Kilgus O., Kinet J. P., Stingl G. Expression of functional high affinity immunoglobulin E receptors (Fc epsilon RI) on monocytes of atopic individuals. J Exp Med. 1994 Feb 1;179(2):745–750. doi: 10.1084/jem.179.2.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Metzger H., Alcaraz G., Hohman R., Kinet J. P., Pribluda V., Quarto R. The receptor with high affinity for immunoglobulin E. Annu Rev Immunol. 1986;4:419–470. doi: 10.1146/annurev.iy.04.040186.002223. [DOI] [PubMed] [Google Scholar]
  24. Montefort S., Gratziou C., Goulding D., Polosa R., Haskard D. O., Howarth P. H., Holgate S. T., Carroll M. P. Bronchial biopsy evidence for leukocyte infiltration and upregulation of leukocyte-endothelial cell adhesion molecules 6 hours after local allergen challenge of sensitized asthmatic airways. J Clin Invest. 1994 Apr;93(4):1411–1421. doi: 10.1172/JCI117118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nagy L., Lee T. H., Kay A. B. Neutrophil chemotactic activity in antigen-induced late asthmatic reactions. N Engl J Med. 1982 Mar 4;306(9):497–501. doi: 10.1056/NEJM198203043060901. [DOI] [PubMed] [Google Scholar]
  26. O'Brien R. M., Thomas W. R., Wootton A. M. T cell responses to the purified major allergens from the house dust mite Dermatophagoides pteronyssinus. J Allergy Clin Immunol. 1992 May;89(5):1021–1031. doi: 10.1016/0091-6749(92)90225-q. [DOI] [PubMed] [Google Scholar]
  27. Plaut M., Pierce J. H., Watson C. J., Hanley-Hyde J., Nordan R. P., Paul W. E. Mast cell lines produce lymphokines in response to cross-linkage of Fc epsilon RI or to calcium ionophores. Nature. 1989 May 4;339(6219):64–67. doi: 10.1038/339064a0. [DOI] [PubMed] [Google Scholar]
  28. Robertson M. W., Albrandt K., Keller D., Liu F. T. Human IgE-binding protein: a soluble lectin exhibiting a highly conserved interspecies sequence and differential recognition of IgE glycoforms. Biochemistry. 1990 Sep 4;29(35):8093–8100. doi: 10.1021/bi00487a015. [DOI] [PubMed] [Google Scholar]
  29. Sastre J., Banks D. E., Lopez M., Barkman H. W., Salvaggio J. E. Neutrophil chemotactic activity in toluene diisocyanate (TDI)-induced asthma. J Allergy Clin Immunol. 1990 Mar;85(3):567–572. doi: 10.1016/0091-6749(90)90094-k. [DOI] [PubMed] [Google Scholar]
  30. Secrist H., Chelen C. J., Wen Y., Marshall J. D., Umetsu D. T. Allergen immunotherapy decreases interleukin 4 production in CD4+ T cells from allergic individuals. J Exp Med. 1993 Dec 1;178(6):2123–2130. doi: 10.1084/jem.178.6.2123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thelen M., Dewald B., Baggiolini M. Neutrophil signal transduction and activation of the respiratory burst. Physiol Rev. 1993 Oct;73(4):797–821. doi: 10.1152/physrev.1993.73.4.797. [DOI] [PubMed] [Google Scholar]
  32. Truong M. J., Gruart V., Kusnierz J. P., Papin J. P., Loiseau S., Capron A., Capron M. Human neutrophils express immunoglobulin E (IgE)-binding proteins (Mac-2/epsilon BP) of the S-type lectin family: role in IgE-dependent activation. J Exp Med. 1993 Jan 1;177(1):243–248. doi: 10.1084/jem.177.1.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wang J. F., Komarov P., de Groot H. Luminol chemiluminescence in rat macrophages and granulocytes: the role of NO, O2-/H2O2, and HOCl. Arch Biochem Biophys. 1993 Jul;304(1):189–196. doi: 10.1006/abbi.1993.1338. [DOI] [PubMed] [Google Scholar]
  34. Weiss S. J. Tissue destruction by neutrophils. N Engl J Med. 1989 Feb 9;320(6):365–376. doi: 10.1056/NEJM198902093200606. [DOI] [PubMed] [Google Scholar]
  35. Wollenberg A., de la Salle H., Hanau D., Liu F. T., Bieber T. Human keratinocytes release the endogenous beta-galactoside-binding soluble lectin immunoglobulin E (IgE-binding protein) which binds to Langerhans cells where it modulates their binding capacity for IgE glycoforms. J Exp Med. 1993 Sep 1;178(3):777–785. doi: 10.1084/jem.178.3.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yamaoka A., Kuwabara I., Frigeri L. G., Liu F. T. A human lectin, galectin-3 (epsilon bp/Mac-2), stimulates superoxide production by neutrophils. J Immunol. 1995 Apr 1;154(7):3479–3487. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES