Granzyme B, a novel mediator of allergic inflammation: its induction and release in blood basophils and human asthma

Tschopp, Cornelia M; Spiegl, Nicole; Didichenko, Svetlana; Lutmann, Werner; Julius, Peter; Virchow, J Christian; Hack, C Erik; Dahinden, Clemens A (2006). Granzyme B, a novel mediator of allergic inflammation: its induction and release in blood basophils and human asthma. Blood, 108(7), pp. 2290-9. Washington, D.C.: American Society of Hematology 10.1182/blood-2006-03-010348

Full text not available from this repository.

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 makeup 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 to 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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute for Immunology [discontinued]
UniBE Contributor:	Dahinden, Clemens A.
ISSN:	0006-4971
ISBN:	16794249
Publisher:	American Society of Hematology
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:46
Last Modified:	05 Dec 2022 14:14
Publisher DOI:	10.1182/blood-2006-03-010348
PubMed ID:	16794249
Web of Science ID:	000240848700030
URI:	https://boris.unibe.ch/id/eprint/19110 (FactScience: 1481)