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Current Topics in Pharmacology   Volumes    Volume 10  Issue 2
Anaphylatoxin C5a as a target for a novel anti-asthmatic treatment
Masayoshi Abe
Pages: 31 - 40
Number of pages: 10
Current Topics in Pharmacology
Volume 10  Issue 2

Copyright © 2006 Research Trends. All rights reserved

The complement system not only plays an important role in the defense system, but also contributes to the amplification of inflammation if activated in excess or inappropriately controlled. Complement activation through any of the three pathways is tightly controlled, effectively restricting excessive activity by the various regulators of complement activation (RCA) constitutively expressed on various cells. Complement activation produces anaphylatoxic polypeptides, as well as the membrane attack complex (MAC) which has a large molecular mass. The anaphylatoxins C3a, C4a, and C5a are considered to bridge innate and acquired immunity. Complement activation may contribute to the pathophysiology of asthma in a dual manner: C5a/C5a receptor signaling may have a suppressive effect through the Th2-skewing of naive T cells during sensitization to an allergen, but may also have a considerable proinflammatory effect in promoting and amplifying asthmatic symptoms in established allergic individuals. Pharmacological manipulation of the complement system may involve various strategies such as use of 1) receptor antagonists of the anaphylatoxins C5a and C3a, 2) inhibitors of C5a including monoclonal antibody, and 3) inhibitors of complement activation at the respective levels. Although control of C5a/C5aR signaling with certain drug may act as a double-edged sword as has been the case with steroids, anaphylatoxin C5a will continue to be a useful target for the development of novel anti-asthmatic therapies.
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