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Cutting edge: Guinea pigs with a natural C3a-receptor defect exhibit decreased bronchoconstriction in allergic airway disease: Evidence for an involvement of the C3a anaphylatoxin in the pathogenesis of asthma

: Bautsch, W.; Hoymann, H.-G.; Zhang, Q.; Meier-Wiedenbach, I.; Raschke, U.; Ames, R.S.; Sohns, B.; Flemme, N.; Meyer zu Vilsendorf, A.; Grove, M.; Klos, A.; Köhl, J.

The Journal of immunology 165 (2000), Nr.10, S.5401-5405
ISSN: 0022-1767
ISSN: 1048-3233
ISSN: 1047-7381
ISSN: 1550-6606
Fraunhofer ITA ( ITEM) ()
ovalbumine; analphylatoxins; Asthma; allergy; Guinea pig; in vivo; interleukin

Asthma is a major cause of morbidity worldwide with prevalence and severity still increasing at an alarming pace. Hallmarks of this disease include early-phase bronchoconstriction with subsequent eosinophil infiltration, symptoms that may be mimicked in vivo by the complement-derived C3a anaphylatoxin, following its interaction with the single-copy C3aR. We analyzed the pathophysiological role of the C3a anaphylatoxin in a model of experimental OVA-induced allergic asthma, using an inbred guinea pig strain phenotypically unresponsive to C3a. Molecular analysis of this defect revealed a point mutation within the coding region of the C3aR that creates a stop codon, thereby effectively inactivating gene function. When challenged by OVA inhalation, sensitized animals of this strain exhibited a bronchoconstriction decreased by approximately 30 % in comparison to the corresponding wild-type strain. These data suggest an important role of C3a in the pathogenesis of asthma and define a novel target for drug intervention strategies.