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Plasma contact system activation drives anaphylaxis in severe mast cell-mediated allergic reactions

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Plasma contact system activation drives anaphylaxis in severe mast cell-mediated allergic reactions. / Sala-Cunill, Anna; Björkqvist, Jenny; Senter, Riccardo; Guilarte, Mar; Cardona, Victoria; Labrador, Moises; Nickel, Katrin F; Butler, Lynn; Luengo, Olga; Kumar, Parvin; Labberton, Linda; Long, Andy; Di Gennaro, Antonio; Kenne, Ellinor; Jämsä, Anne; Krieger, Thorsten; Schlüter, Hartmut; Fuchs, Tobias; Flohr, Stefanie; Hassiepen, Ulrich; Cumin, Frederic; McCrae, Keith; Maas, Coen; Stavrou, Evi; Renné, Thomas.

In: J ALLERGY CLIN IMMUN, Vol. 135, No. 4, 01.04.2015, p. 1031-1043.e6.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sala-Cunill, A, Björkqvist, J, Senter, R, Guilarte, M, Cardona, V, Labrador, M, Nickel, KF, Butler, L, Luengo, O, Kumar, P, Labberton, L, Long, A, Di Gennaro, A, Kenne, E, Jämsä, A, Krieger, T, Schlüter, H, Fuchs, T, Flohr, S, Hassiepen, U, Cumin, F, McCrae, K, Maas, C, Stavrou, E & Renné, T 2015, 'Plasma contact system activation drives anaphylaxis in severe mast cell-mediated allergic reactions', J ALLERGY CLIN IMMUN, vol. 135, no. 4, pp. 1031-1043.e6. https://doi.org/10.1016/j.jaci.2014.07.057

APA

Sala-Cunill, A., Björkqvist, J., Senter, R., Guilarte, M., Cardona, V., Labrador, M., Nickel, K. F., Butler, L., Luengo, O., Kumar, P., Labberton, L., Long, A., Di Gennaro, A., Kenne, E., Jämsä, A., Krieger, T., Schlüter, H., Fuchs, T., Flohr, S., ... Renné, T. (2015). Plasma contact system activation drives anaphylaxis in severe mast cell-mediated allergic reactions. J ALLERGY CLIN IMMUN, 135(4), 1031-1043.e6. https://doi.org/10.1016/j.jaci.2014.07.057

Vancouver

Sala-Cunill A, Björkqvist J, Senter R, Guilarte M, Cardona V, Labrador M et al. Plasma contact system activation drives anaphylaxis in severe mast cell-mediated allergic reactions. J ALLERGY CLIN IMMUN. 2015 Apr 1;135(4):1031-1043.e6. https://doi.org/10.1016/j.jaci.2014.07.057

Bibtex

@article{0d2a80dd6e7f424aad43930da0f1bc8b,
title = "Plasma contact system activation drives anaphylaxis in severe mast cell-mediated allergic reactions",
abstract = "BACKGROUND: Anaphylaxis is an acute, potentially lethal, multisystem syndrome resulting from the sudden release of mast cell-derived mediators into the circulation.OBJECTIVES AND METHODS: We report here that a plasma protease cascade, the factor XII-driven contact system, critically contributes to the pathogenesis of anaphylaxis in both murine models and human subjects.RESULTS: Deficiency in or pharmacologic inhibition of factor XII, plasma kallikrein, high-molecular-weight kininogen, or the bradykinin B2 receptor, but not the B1 receptor, largely attenuated allergen/IgE-mediated mast cell hyperresponsiveness in mice. Reconstitutions of factor XII null mice with human factor XII restored susceptibility for allergen/IgE-mediated hypotension. Activated mast cells systemically released heparin, which provided a negatively charged surface for factor XII autoactivation. Activated factor XII generates plasma kallikrein, which proteolyzes kininogen, leading to the liberation of bradykinin. We evaluated the contact system in patients with anaphylaxis. In all 10 plasma samples immunoblotting revealed activation of factor XII, plasma kallikrein, and kininogen during the acute phase of anaphylaxis but not at basal conditions or in healthy control subjects. The severity of anaphylaxis was associated with mast cell degranulation, increased plasma heparin levels, the intensity of contact system activation, and bradykinin formation.CONCLUSIONS: In summary, the data collectively show a role of the contact system in patients with anaphylaxis and support the hypothesis that targeting bradykinin generation and signaling provides a novel and alternative treatment strategy for anaphylactic attacks.",
author = "Anna Sala-Cunill and Jenny Bj{\"o}rkqvist and Riccardo Senter and Mar Guilarte and Victoria Cardona and Moises Labrador and Nickel, {Katrin F} and Lynn Butler and Olga Luengo and Parvin Kumar and Linda Labberton and Andy Long and {Di Gennaro}, Antonio and Ellinor Kenne and Anne J{\"a}ms{\"a} and Thorsten Krieger and Hartmut Schl{\"u}ter and Tobias Fuchs and Stefanie Flohr and Ulrich Hassiepen and Frederic Cumin and Keith McCrae and Coen Maas and Evi Stavrou and Thomas Renn{\'e}",
note = "Copyright {\textcopyright} 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.",
year = "2015",
month = apr,
day = "1",
doi = "10.1016/j.jaci.2014.07.057",
language = "English",
volume = "135",
pages = "1031--1043.e6",
journal = "J ALLERGY CLIN IMMUN",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "4",

}

RIS

TY - JOUR

T1 - Plasma contact system activation drives anaphylaxis in severe mast cell-mediated allergic reactions

AU - Sala-Cunill, Anna

AU - Björkqvist, Jenny

AU - Senter, Riccardo

AU - Guilarte, Mar

AU - Cardona, Victoria

AU - Labrador, Moises

AU - Nickel, Katrin F

AU - Butler, Lynn

AU - Luengo, Olga

AU - Kumar, Parvin

AU - Labberton, Linda

AU - Long, Andy

AU - Di Gennaro, Antonio

AU - Kenne, Ellinor

AU - Jämsä, Anne

AU - Krieger, Thorsten

AU - Schlüter, Hartmut

AU - Fuchs, Tobias

AU - Flohr, Stefanie

AU - Hassiepen, Ulrich

AU - Cumin, Frederic

AU - McCrae, Keith

AU - Maas, Coen

AU - Stavrou, Evi

AU - Renné, Thomas

N1 - Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - BACKGROUND: Anaphylaxis is an acute, potentially lethal, multisystem syndrome resulting from the sudden release of mast cell-derived mediators into the circulation.OBJECTIVES AND METHODS: We report here that a plasma protease cascade, the factor XII-driven contact system, critically contributes to the pathogenesis of anaphylaxis in both murine models and human subjects.RESULTS: Deficiency in or pharmacologic inhibition of factor XII, plasma kallikrein, high-molecular-weight kininogen, or the bradykinin B2 receptor, but not the B1 receptor, largely attenuated allergen/IgE-mediated mast cell hyperresponsiveness in mice. Reconstitutions of factor XII null mice with human factor XII restored susceptibility for allergen/IgE-mediated hypotension. Activated mast cells systemically released heparin, which provided a negatively charged surface for factor XII autoactivation. Activated factor XII generates plasma kallikrein, which proteolyzes kininogen, leading to the liberation of bradykinin. We evaluated the contact system in patients with anaphylaxis. In all 10 plasma samples immunoblotting revealed activation of factor XII, plasma kallikrein, and kininogen during the acute phase of anaphylaxis but not at basal conditions or in healthy control subjects. The severity of anaphylaxis was associated with mast cell degranulation, increased plasma heparin levels, the intensity of contact system activation, and bradykinin formation.CONCLUSIONS: In summary, the data collectively show a role of the contact system in patients with anaphylaxis and support the hypothesis that targeting bradykinin generation and signaling provides a novel and alternative treatment strategy for anaphylactic attacks.

AB - BACKGROUND: Anaphylaxis is an acute, potentially lethal, multisystem syndrome resulting from the sudden release of mast cell-derived mediators into the circulation.OBJECTIVES AND METHODS: We report here that a plasma protease cascade, the factor XII-driven contact system, critically contributes to the pathogenesis of anaphylaxis in both murine models and human subjects.RESULTS: Deficiency in or pharmacologic inhibition of factor XII, plasma kallikrein, high-molecular-weight kininogen, or the bradykinin B2 receptor, but not the B1 receptor, largely attenuated allergen/IgE-mediated mast cell hyperresponsiveness in mice. Reconstitutions of factor XII null mice with human factor XII restored susceptibility for allergen/IgE-mediated hypotension. Activated mast cells systemically released heparin, which provided a negatively charged surface for factor XII autoactivation. Activated factor XII generates plasma kallikrein, which proteolyzes kininogen, leading to the liberation of bradykinin. We evaluated the contact system in patients with anaphylaxis. In all 10 plasma samples immunoblotting revealed activation of factor XII, plasma kallikrein, and kininogen during the acute phase of anaphylaxis but not at basal conditions or in healthy control subjects. The severity of anaphylaxis was associated with mast cell degranulation, increased plasma heparin levels, the intensity of contact system activation, and bradykinin formation.CONCLUSIONS: In summary, the data collectively show a role of the contact system in patients with anaphylaxis and support the hypothesis that targeting bradykinin generation and signaling provides a novel and alternative treatment strategy for anaphylactic attacks.

U2 - 10.1016/j.jaci.2014.07.057

DO - 10.1016/j.jaci.2014.07.057

M3 - SCORING: Journal article

C2 - 25240785

VL - 135

SP - 1031-1043.e6

JO - J ALLERGY CLIN IMMUN

JF - J ALLERGY CLIN IMMUN

SN - 0091-6749

IS - 4

ER -