Recent experiments performed with up-to-date molecular biological techniques indicate that complement has a major role in the sensitization of patients to different allergens. Karp et al. (14) compared two groups of inbred mouse strains that exhibited low and high responsiveness to metacholine challenge. They have demonstrated that the C5 gene conferred decreased bronchial responsiveness following allergen challenge: responsiveness of the genetically C5-deficient strains was significantly higher than that in the C5 sufficient animals. Authors explained their finding with the ability of C5a to inhibit IL-12 release from monocytes and macrophages and the consequent Th1 response. When C5 is absent, that is, no C5a can be generated, the balance of immune response switches toward the Th2 type response that is characteristic of allergy. In accordance with this observation, at genome-wide scanning of asthma susceptibility loci it was found that among the asthma-associated genetic regions the C5 gene in chromosome 9 and that for the C5a receptor in chromosome 19 (15,16,17) are present.
In contrast to the results obtained with C5, Drouin et al. demonstrated that C3 (18) and the C3a receptors (C3aR) (19) are necessary for an effective Th2 type response to occur after allergen challenge. Mice deficient in C3a exhibited not only a diminished airway hyperresponsiveness and lung eosonophilia after intranasal challenge with Aspergillus fumigatus + BSA allergen (see below), but they had a dramatically reduced numbers of IL-4 producing cells and attenuated IgE and IgG1 responses (18). Similarly, C3aR knock out mice had an 59% reduction of IL-4 producing cells, diminished levels of Th2 type cytokines IL-5 and IL-13 in bronchoalveolar lavage fluid, decreased IgE titers and reduced mucus production (19). These data implicate C3a and its receptor in the Th2 response development in this model and indicate a role of the complement system in sensitization stage by promoting Th2 effector functions in asthma and other types of allergic diseases.
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