New insights into the role of the complement pathway in allergy and asthma.
Despite extensive inquiry, the mechanisms underlying the pathophysiology of allergic diseases remain unknown. Recently, there has been a resurgence of interest in the role of the innate immune mediators of the complement pathway in asthma pathogenesis, particularly the anaphylatoxins (C3a, C5a). The emerging paradigm is that C3a production at the airway surface serves as a common pathway for the induction of airway hyperresponsiveness to a variety of asthma triggers (ie, allergens, viral infections, particulate matter, ozone, smoke), whereas C5/C5a plays a dual immunoregulatory role by protecting against Th2-mediated immune responses during initiation of responses and a proinflammatory role once immune responses are established. Support for a causal role for altered anaphylatoxin production in human disease comes from reports of exaggerated complement production in the lungs of asthmatics as well as the association of asthma with polymorphisms in C3/C3aR genes. Herein, we explore our current understanding of the role of complement activation in asthma pathogenesis and highlight the potential of targeting complement pathways for therapeutic drug development.
Wills-Karp
Marsha
M
Division of Immunobiology, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. wildc7@chmcc.org
Koehl
Joerg
J
D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology*; D003167:Complement Activation; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*