title: The anaphylatoxins bridge innate and adaptive immune responses in allergic asthma.
abstract: The complement system has long been recognized for its role as a lytic effector system that protects against microbial pathogens, as well as for its role in mediating acute and chronic inflammatory responses. Many of the inflammatory sequelae of complement activation can be related to the complement cleavage fragments C3a and C5a, the so-called anaphylatoxins (ATs). Cloning and subsequent gene targeting of their corresponding receptors, as well as generation of specific C3a and C5a inhibitors, have fueled new interest in studies aimed at defining the roles of the anaphylatoxins in inflammatory diseases. Traditionally, the anaphylatoxins have been considered mediators of end-stage effector mechanisms. However, recent data from animal models of allergic asthma suggest that C3a and C5a provide a critical link between innate and adaptive immunity. This review is aimed at outlining our current knowledge of when and where anaphylatoxins contribute to and control the development of allergic asthma. The accumulated data suggest a model in which C3a and C5a play important but opposing roles during allergen-induced T-cell polarization: C3a promotes Th2 responses, whereas C5a prevents Th2 polarization. During the effector phase, both anaphylatoxins trigger the inflammatory response and contribute to bronchoconstriction.
authors.affiliation: Division of Molecular Immunology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
authors.forename: Heiko
authors.initials: H
authors.lastname: Hawlisch
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Karp
authors.forename: Jörg
authors.initials: J
authors.lastname: Köhl
mesh_terms: D000485:Allergens / Q000276:immunology; D000706:Anaphylatoxins / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: D000485:Allergens; D000706:Anaphylatoxins; D003165:Complement System Proteins