Bautsch, W.W.BautschHoymann, H.-G.H.-G.HoymannZhang, Q.Q.ZhangMeier-Wiedenbach, I.I.Meier-WiedenbachRaschke, U.U.RaschkeAmes, R.S.R.S.AmesSohns, B.B.SohnsFlemme, N.N.FlemmeMeyer zu Vilsendorf, A.A.Meyer zu VilsendorfGrove, M.M.GroveKlos, A.A.KlosKöhl, J.J.Köhl2022-03-032022-03-032000https://publica.fraunhofer.de/handle/publica/198251Asthma 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.enovalbumineanalphylatoxinsAsthmaallergyGuinea pigin vivointerleukin615610620journal article