Anaphylatoxin C3a receptors in asthma.
The complement system forms the central core of innate immunity but also mediates a variety of inflammatory responses. Anaphylatoxin C3a, which is generated as a byproduct of complement activation, has long been known to activate mast cells, basophils and eosinophils and to cause smooth muscle contraction. However, the role of C3a in the pathogenesis of allergic asthma remains unclear. In this review, we examine the role of C3a in promoting asthma. Following allergen challenge, C3a is generated in the lung of subjects with asthma but not healthy subjects. Furthermore, deficiency in C3a generation or in G protein coupled receptor for C3a abrogates allergen-induced responses in murine models of pulmonary inflammation and airway hyperresponsiveness. In addition, inhibition of complement activation or administration of small molecule inhibitors of C3a receptor after sensitization but before allergen challenge inhibits airway responses. At a cellular level, C3a stimulates robust mast cell degranulation that is greatly enhanced following cell-cell contact with airway smooth muscle (ASM) cells. Therefore, C3a likely plays an important role in asthma primarily by regulating mast cell-ASM cell interaction.
Ali
Hydar
H
Department of Pathology, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Philadelphia, PA 19104, USA. ali@path.dental.upenn.edu
Panettieri
Reynold A
RA
D000706:Anaphylatoxins / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology*; D015926:Complement C3a / Q000276:immunology*; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D011951:Receptors, Complement / Q000276:immunology*
D000706:Anaphylatoxins; D008565:Membrane Proteins; D011951:Receptors, Complement; C085567:complement C3a receptor; D015926:Complement C3a
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