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. 1996 Apr 1;97(7):1761–1766. doi: 10.1172/JCI118603

CD40 expression by human peripheral blood eosinophils.

Y Ohkawara 1, K G Lim 1, Z Xing 1, M Glibetic 1, K Nakano 1, J Dolovich 1, K Croitoru 1, P F Weller 1, M Jordana 1
PMCID: PMC507241  PMID: 8601642

Abstract

In this study, we have investigated CD40 expression in human peripheral blood eosinophils and in human chronically inflamed nasal tissues, i.e., nasal polyps. We show by both reverse transcriptase-PCR and Northern blot analysis that eosinophils from allergic subjects express human CD40 mRNA. We also show that constitutive CD40 mRNA expression in eosinophils could be upregulated by exposure to IgA immune complexes and downregulated by IL-10 and the synthetic steroid budesonide. In addition, we demonstrate that eosinophils express CD40 protein by flow cytometry. Such expression is biologically functional as cross-linking CD40 with CD40 mAbs enhances eosinophil survival in a dose-dependent fashion; in addition, CD40 ligation stimulates eosinophils to release GM-CSF. CD40-mediated eosinophil survival was largely inhibited by an anti-GM-CSF neutralizing antibody suggesting GM-CSF involvement in the survival enhancing mechanism. CD40 mRNA was also detected in total RNA extracted from nasal polyp tissues but not in RNA isolated from normal nasal mucosa (inferior turbinate); by immunohistochemistry, we were able to detect immunoreactive CD40 protein in a variety of cell types in the polyp stroma, but primarily in eosinophils. These observations suggest previously unforeseen interactions between eosinophils and cells expressing the CD40 ligand and, thus, novel pathways by which eosinophils may contribute to the regulation of airway inflammation.

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Selected References

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  1. Abu-Ghazaleh R. I., Fujisawa T., Mestecky J., Kyle R. A., Gleich G. J. IgA-induced eosinophil degranulation. J Immunol. 1989 Apr 1;142(7):2393–2400. [PubMed] [Google Scholar]
  2. Alderson M. R., Armitage R. J., Tough T. W., Strockbine L., Fanslow W. C., Spriggs M. K. CD40 expression by human monocytes: regulation by cytokines and activation of monocytes by the ligand for CD40. J Exp Med. 1993 Aug 1;178(2):669–674. doi: 10.1084/jem.178.2.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Caux C., Massacrier C., Vanbervliet B., Dubois B., Van Kooten C., Durand I., Banchereau J. Activation of human dendritic cells through CD40 cross-linking. J Exp Med. 1994 Oct 1;180(4):1263–1272. doi: 10.1084/jem.180.4.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Clark E. A. CD40: a cytokine receptor in search of a ligand. Tissue Antigens. 1990 Jul;36(1):33–36. doi: 10.1111/j.1399-0039.1990.tb01795.x. [DOI] [PubMed] [Google Scholar]
  6. Cox G., Ohtoshi T., Vancheri C., Denburg J. A., Dolovich J., Gauldie J., Jordana M. Promotion of eosinophil survival by human bronchial epithelial cells and its modulation by steroids. Am J Respir Cell Mol Biol. 1991 Jun;4(6):525–531. doi: 10.1165/ajrcmb/4.6.525. [DOI] [PubMed] [Google Scholar]
  7. Dubucquoi S., Desreumaux P., Janin A., Klein O., Goldman M., Tavernier J., Capron A., Capron M. Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion. J Exp Med. 1994 Feb 1;179(2):703–708. doi: 10.1084/jem.179.2.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Durie F. H., Aruffo A., Ledbetter J., Crassi K. M., Green W. R., Fast L. D., Noelle R. J. Antibody to the ligand of CD40, gp39, blocks the occurrence of the acute and chronic forms of graft-vs-host disease. J Clin Invest. 1994 Sep;94(3):1333–1338. doi: 10.1172/JCI117453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Durie F. H., Fava R. A., Foy T. M., Aruffo A., Ledbetter J. A., Noelle R. J. Prevention of collagen-induced arthritis with an antibody to gp39, the ligand for CD40. Science. 1993 Sep 3;261(5126):1328–1330. doi: 10.1126/science.7689748. [DOI] [PubMed] [Google Scholar]
  10. Fries K. M., Sempowski G. D., Gaspari A. A., Blieden T., Looney R. J., Phipps R. P. CD40 expression by human fibroblasts. Clin Immunol Immunopathol. 1995 Oct;77(1):42–51. doi: 10.1016/0090-1229(95)90135-3. [DOI] [PubMed] [Google Scholar]
  11. Galy A. H., Spits H. CD40 is functionally expressed on human thymic epithelial cells. J Immunol. 1992 Aug 1;149(3):775–782. [PubMed] [Google Scholar]
  12. Gauchat J. F., Henchoz S., Fattah D., Mazzei G., Aubry J. P., Jomotte T., Dash L., Page K., Solari R., Aldebert D. CD40 ligand is functionally expressed on human eosinophils. Eur J Immunol. 1995 Mar;25(3):863–865. doi: 10.1002/eji.1830250335. [DOI] [PubMed] [Google Scholar]
  13. Gauchat J. F., Henchoz S., Mazzei G., Aubry J. P., Brunner T., Blasey H., Life P., Talabot D., Flores-Romo L., Thompson J. Induction of human IgE synthesis in B cells by mast cells and basophils. Nature. 1993 Sep 23;365(6444):340–343. doi: 10.1038/365340a0. [DOI] [PubMed] [Google Scholar]
  14. Graf D., Korthäuer U., Mages H. W., Senger G., Kroczek R. A. Cloning of TRAP, a ligand for CD40 on human T cells. Eur J Immunol. 1992 Dec;22(12):3191–3194. doi: 10.1002/eji.1830221226. [DOI] [PubMed] [Google Scholar]
  15. Grammer A. C., Bergman M. C., Miura Y., Fujita K., Davis L. S., Lipsky P. E. The CD40 ligand expressed by human B cells costimulates B cell responses. J Immunol. 1995 May 15;154(10):4996–5010. [PubMed] [Google Scholar]
  16. Holder M. J., Wang H., Milner A. E., Casamayor M., Armitage R., Spriggs M. K., Fanslow W. C., MacLennan I. C., Gregory C. D., Gordon J. Suppression of apoptosis in normal and neoplastic human B lymphocytes by CD40 ligand is independent of Bc1-2 induction. Eur J Immunol. 1993 Sep;23(9):2368–2371. doi: 10.1002/eji.1830230948. [DOI] [PubMed] [Google Scholar]
  17. Hollenbaugh D., Grosmaire L. S., Kullas C. D., Chalupny N. J., Braesch-Andersen S., Noelle R. J., Stamenkovic I., Ledbetter J. A., Aruffo A. The human T cell antigen gp39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co-stimulatory activity. EMBO J. 1992 Dec;11(12):4313–4321. doi: 10.1002/j.1460-2075.1992.tb05530.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hollenbaugh D., Mischel-Petty N., Edwards C. P., Simon J. C., Denfeld R. W., Kiener P. A., Aruffo A. Expression of functional CD40 by vascular endothelial cells. J Exp Med. 1995 Jul 1;182(1):33–40. doi: 10.1084/jem.182.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Liu Y. J., Joshua D. E., Williams G. T., Smith C. A., Gordon J., MacLennan I. C. Mechanism of antigen-driven selection in germinal centres. Nature. 1989 Dec 21;342(6252):929–931. doi: 10.1038/342929a0. [DOI] [PubMed] [Google Scholar]
  20. Lopez A. F., Williamson D. J., Gamble J. R., Begley C. G., Harlan J. M., Klebanoff S. J., Waltersdorph A., Wong G., Clark S. C., Vadas M. A. Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival. J Clin Invest. 1986 Nov;78(5):1220–1228. doi: 10.1172/JCI112705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mohan C., Shi Y., Laman J. D., Datta S. K. Interaction between CD40 and its ligand gp39 in the development of murine lupus nephritis. J Immunol. 1995 Feb 1;154(3):1470–1480. [PubMed] [Google Scholar]
  22. Nonaka M., Nonaka R., Woolley K., Adelroth E., Miura K., Okhawara Y., Glibetic M., Nakano K., O'Byrne P., Dolovich J. Distinct immunohistochemical localization of IL-4 in human inflamed airway tissues. IL-4 is localized to eosinophils in vivo and is released by peripheral blood eosinophils. J Immunol. 1995 Sep 15;155(6):3234–3244. [PubMed] [Google Scholar]
  23. Owen W. F., Jr, Rothenberg M. E., Silberstein D. S., Gasson J. C., Stevens R. L., Austen K. F., Soberman R. J. Regulation of human eosinophil viability, density, and function by granulocyte/macrophage colony-stimulating factor in the presence of 3T3 fibroblasts. J Exp Med. 1987 Jul 1;166(1):129–141. doi: 10.1084/jem.166.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Paulie S., Ehlin-Henriksson B., Mellstedt H., Koho H., Ben-Aissa H., Perlmann P. A p50 surface antigen restricted to human urinary bladder carcinomas and B lymphocytes. Cancer Immunol Immunother. 1985;20(1):23–28. doi: 10.1007/BF00199769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schall T. J., Lewis M., Koller K. J., Lee A., Rice G. C., Wong G. H., Gatanaga T., Granger G. A., Lentz R., Raab H. Molecular cloning and expression of a receptor for human tumor necrosis factor. Cell. 1990 Apr 20;61(2):361–370. doi: 10.1016/0092-8674(90)90816-w. [DOI] [PubMed] [Google Scholar]
  26. Smith C. A., Davis T., Anderson D., Solam L., Beckmann M. P., Jerzy R., Dower S. K., Cosman D., Goodwin R. G. A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science. 1990 May 25;248(4958):1019–1023. doi: 10.1126/science.2160731. [DOI] [PubMed] [Google Scholar]
  27. Spriggs M. K., Armitage R. J., Strockbine L., Clifford K. N., Macduff B. M., Sato T. A., Maliszewski C. R., Fanslow W. C. Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion. J Exp Med. 1992 Dec 1;176(6):1543–1550. doi: 10.1084/jem.176.6.1543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stamenkovic I., Clark E. A., Seed B. A B-lymphocyte activation molecule related to the nerve growth factor receptor and induced by cytokines in carcinomas. EMBO J. 1989 May;8(5):1403–1410. doi: 10.1002/j.1460-2075.1989.tb03521.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tomassini M., Tsicopoulos A., Tai P. C., Gruart V., Tonnel A. B., Prin L., Capron A., Capron M. Release of granule proteins by eosinophils from allergic and nonallergic patients with eosinophilia on immunoglobulin-dependent activation. J Allergy Clin Immunol. 1991 Sep;88(3 Pt 1):365–375. doi: 10.1016/0091-6749(91)90099-a. [DOI] [PubMed] [Google Scholar]
  30. Valent P., Majdic O., Maurer D., Bodger M., Muhm M., Bettelheim P. Further characterization of surface membrane structures expressed on human basophils and mast cells. Int Arch Allergy Appl Immunol. 1990;91(2):198–203. doi: 10.1159/000235115. [DOI] [PubMed] [Google Scholar]
  31. Yellin M. J., Winikoff S., Fortune S. M., Baum D., Crow M. K., Lederman S., Chess L. Ligation of CD40 on fibroblasts induces CD54 (ICAM-1) and CD106 (VCAM-1) up-regulation and IL-6 production and proliferation. J Leukoc Biol. 1995 Aug;58(2):209–216. doi: 10.1002/jlb.58.2.209. [DOI] [PubMed] [Google Scholar]

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