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

• Published in: The Journal of immunology (1950) Vol. 165; no. 10; pp. 5401 - 5405
• Main Authors: Bautsch, Wilfried, Hoymann, Heinz-Gerd, Zhang, Qiuwang, Meier-Wiedenbach, Ivo, Raschke, Ursula, Ames, Robert S, Sohns, Bettina, Flemme, Nicole, Meyer zu Vilsendorf, Andreas, Grove, Melanie, Klos, Andreas, Kohl, Jorg
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-11-2000
• Subjects: Administration, Inhalation; Airway Resistance - genetics; Airway Resistance - immunology; Animals; Asthma - etiology; Asthma - immunology; Asthma - pathology; Bronchoconstriction - immunology; Cell Line; Cell Movement - immunology; Complement C3a - metabolism; Complement C3a - physiology; Eosinophils - pathology; Gene Expression Regulation - immunology; Genetic Markers - immunology; Guinea Pigs; Humans; Injections, Intraperitoneal; Membrane Proteins; Ovalbumin - administration & dosage; Ovalbumin - immunology; Point Mutation - immunology; Receptors, Complement - antagonists & inhibitors; Receptors, Complement - deficiency; Receptors, Complement - genetics; Species Specificity; Up-Regulation - genetics; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.10.5401

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.