A role for the c3a anaphylatoxin receptor in the effector phase of asthma

ABSTRACT Asthma is a chronic inflammatory disease of the airways and lung mucosa with a strong correlation to atopy and acquired (IgE) immunity1. However, many features of bronchial asthma,

such as smooth muscle contraction, mucus secretion and recruitment of inflammatory cells, are consistent with the actions of complement anaphylatoxins, in particular C3a and C5a2. Complement

activation forms a central core of innate immune defence against mucosal bacteria, viruses, fungi, helminths and other pathogens. As a system of ‘pattern-recognition molecules’, foreign

surface antigens and immune complexes lead to a proteolytic cascade culminating in a lytic membrane attack2,3. The anaphylatoxins C3a and C5a are liberated as activation byproducts and are

potent pro-inflammatory mediators that bind to specific cell surface receptors and cause leukocyte activation, smooth muscle contraction and vascular permeability2. Here we show that in a

murine model of allergic airway disease, genetic deletion of the C3a receptor protects against the changes in lung physiology seen after allergen challenge. Furthermore, human asthmatics

develop significant levels of ligand C3a following intra-pulmonary deposition of allergen, but not saline. We propose that, in addition to acquired immune responses, the innate immune system

and complement (C3a in particular) are involved in the pathogenesis of asthma. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS REVEALING THE SIGNALING OF COMPLEMENT RECEPTORS C3AR AND C5AR1 BY

ANAPHYLATOXINS Article 11 May 2023 TYPE 2 IMMUNITY IN ALLERGIC DISEASES Article Open access 17 February 2025 THE OUROBOROS OF AUTOIMMUNITY Article 02 May 2024 REFERENCES * Burrows, B.,

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advice; J. Brewer for assistance; D. Zurakowski for help and advice with analysing the statistics; and the staff of ARCH at Children's Hospital for animal care. This work was supported

in part by grants from the NIH to N.P.G. and C.G. at the Perlmutter laboratory and Pfizer Central Research. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Ina Sue Perlmutter Laboratory,

Children's Hospital, Harvard Medical School, Boston, 02115, Massachusetts , USA Alison A. Humbles, Bao Lu, Christy A. Nilsson, Norma P. Gerard & Craig Gerard * Division of Pulmonary

and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA Craig Lilly & Elliot Israel * Division of Hematology and

Oncology Children's Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA Yuko Fujiwara Authors * Alison A. Humbles View author publications You can also search for this

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AUTHOR Correspondence to Craig Gerard. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Humbles, A., Lu, B., Nilsson, C. _et al._ A role for the C3a

anaphylatoxin receptor in the effector phase of asthma . _Nature_ 406, 998–1001 (2000). https://doi.org/10.1038/35023175 Download citation * Received: 17 May 2000 * Accepted: 18 July 2000 *

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