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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2290-2299. Prepublished online as a Blood First Edition Paper on June 27, 2006June 22, 2006; DOI 10.1182/blood-2006-03-010348. This Article Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2006-03-010348v1 blood-2006-03-010348v2 108/7/2290    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tschopp, C. M Articles by Dahinden, C. A Search for Related Content PubMed PubMed Citation Articles by Tschopp, C. M Articles by Dahinden, C. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 15, 2006 Accepted May 24, 2006 Granzyme B, a novel mediator of allergic inflammation: Its induction and release in blood basophils and human asthma Cornelia M Tschopp, Nicole Spiegl, Svetlana Didichenko, Werner Lutmann, Peter Julius, J C Virchow, C E Hack, and Clemens A Dahinden* Institute of Immunology, Inselspital, University of Bern, Switzerland Department of Pneumology, University Medical Clinic, Rostock, Germany Sanquin Research at the CLB, Amsterdam, the Netherlands University Hospital * Corresponding author; email: clemens.dahinden{at}iib.unibe.ch. Histamine, leukotriene-C4, IL-4 and IL-13 are major mediators of allergy and asthma. They are all formed by basophils and are released in particularly large quantities after stimulation with IL-3. Here we show that supernatants of activated mast cells or IL-3 qualitatively change the make-up of granules of human basophils by inducing de-novo synthesis of granzyme B (GzmB), without induction of other granule proteins expressed by cytotoxic lymphocytes (granzyme A, perforin). This bioactivity of IL-3 is not shared by other cytokines known to regulate the function of basophils or lymphocytes. The IL-3 effect is restricted to basophil granulocytes as no constitutive or inducible expression of GzmB is detected in eosinophils or neutrophils. GzmB is induced within 6-24 hours, sorted into the granule compartment, and released by exocytosis upon IgE-dependent and - independent activation. In vitro, there is a close parallelism between GzmB, IL 13 and leukotriene-C4 production. In vivo, Granzyme B, but not the lymphoid granule marker granzyme A, is released 18 hours after allergen challenge of asthmatic patients in strong correlation with interleukin-13. Our study demonstrates an unexpected plasticity of the granule composition of mature basophils and suggests a role of granzyme B as a novel mediator of allergic diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Pieri, C. Bogani, P. Guglielmelli, M. Zingariello, R. A. Rana, N. Bartalucci, A. Bosi, and A. M. Vannucchi The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils from patients with polycythemia vera Haematologica, November 1, 2009; 94(11): 1537 - 1545. [Abstract] [Full Text] [PDF] K. M. Kroeger, B. M. Sullivan, and R. M. Locksley IL-18 and IL-33 elicit Th2 cytokines from basophils via a MyD88- and p38{alpha}-dependent pathway J. Leukoc. Biol., October 1, 2009; 86(4): 769 - 778. [Abstract] [Full Text] [PDF] D. A. Ngan, S. V. Vickerman, D. J. Granville, S. F. P. Man, and D. D. Sin The possible role of granzyme B in the pathogenesis of chronic obstructive pulmonary disease Therapeutic Advances in Respiratory Disease, June 1, 2009; 3(3): 113 - 129. [Abstract] [PDF] T. Pecaric-Petkovic, S. A. Didichenko, S. Kaempfer, N. Spiegl, and C. A. Dahinden Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33 Blood, February 12, 2009; 113(7): 1526 - 1534. [Abstract] [Full Text] [PDF] S. A. Didichenko, N. Spiegl, T. Brunner, and C. A. Dahinden IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils Blood, November 15, 2008; 112(10): 3949 - 3958. [Abstract] [Full Text] [PDF] K Bratke, A Klug, P Julius, M Kuepper, M Lommatzsch, G Sparmann, W Luttmann, and J C Virchow Granzyme K: a novel mediator in acute airway inflammation Thorax, November 1, 2008; 63(11): 1006 - 1011. [Abstract] [Full Text] [PDF] N. Spiegl, S. Didichenko, P. McCaffery, H. Langen, and C. A. Dahinden Human basophils activated by mast cell-derived IL-3 express retinaldehyde dehydrogenase-II and produce the immunoregulatory mediator retinoic acid Blood, November 1, 2008; 112(9): 3762 - 3771. [Abstract] [Full Text] [PDF]

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