Complement in asthma: sensitivity to activation and generation of C3a and C5a via the different complement pathways.
Studies in rodent models suggested that complement may play a critical role in susceptibility to airway hyperresponsiveness (AHR) and as a mediator of bronchial obstruction and inflammation in asthma. Complement may participate in susceptibility to asthma because of an intrinsic abnormality in complement activation and generation of C3a, C5a, or other products that affect cellular responses, resulting in T(H)2 predominance and asthma susceptibility. Alternatively, an intrinsic abnormality in the cellular response to complement activation products could determine susceptibility to asthma. In this study, the authors investigated whether complement in patients with atopic asthma versus nonatopic controls possesses an increased propensity to become activated. Despite reports that total complement plasma levels in unchallenged asthmatics are normal, an abnormal sensitivity of complement to activation may exist if an isoform or a polymorphic variant of a complement protein was present and resulted in gain or loss of function without associated changes in total complement levels. Therefore, complement activation was induced in vitro in plasma of asthmatics and controls using activators of the classical, alternative, and lectin pathways and measured C3a, other C3 fragments, and C5a. For each pathway, similar amounts of generated fragments, as well as C3a/C3 and C5a/C5 ratios, were found in asthmatics and controls. Also, similar basal plasma levels of C3a and C5a were found in both groups; however, mannan-binding lectin (MBL) levels were moderately elevated in asthmatics. In conclusion, the results suggest that, in asthmatic patients, complement activation does not exhibit an abnormal sensitivity to activation by any of the known activation pathways.
Wust
Sven K
SK
Department of Medicine, School of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Blumenthal
Malcolm N
MN
Corazalla
Edward O
EO
Benson
Barbara A
BA
Dalmasso
Agustin P
AP
D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology; D003167:Complement Activation; D015926:Complement C3a / Q000276:immunology*; D015936:Complement C5a / Q000276:immunology*; D015941:Complement Hemolytic Activity Assay; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology; D005260:Female; D006801:Humans; D012129:Respiratory Function Tests
D015926:Complement C3a; D015936:Complement C5a