A role for the C3a anaphylatoxin receptor in the effector phase of asthma

Asthma is a chronic inflammatory disease of the airways and lung mucosa wit h a strong correlation to atopy and acquired (IgE) immunity(1). However, ma ny features of bronchial asthma, such as smooth muscle contraction, mucus s ecretion and recruitment of inflammatory cells, are consistent with the act ions of complement anaphylatoxins, in particular C3a and C5a(2). Complement activation forms a central core of innate immune defence against mucosal b acteria, viruses, fungi, helminths and other pathogens. As a system of 'pat tern-recognition molecules', foreign surface antigens and immune complexes lead to a proteolytic cascade culminating in a lytic membrane attack(2,3). The anaphylatoxins C3a and C5a are liberated as activation byproducts and a re potent pro-inflammatory mediators that bind to specific cell surface rec eptors and cause leukocyte activation, smooth muscle contraction and vascul ar permeability(2). 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 asthma tics develop significant levels of ligand C3a following intra-pulmonary dep osition of allergen, but not saline. We propose that, in addition to acquir ed immune responses, the innate immune system and complement (C3a in partic ular) are involved in the pathogenesis of asthma.