Complement in animal studies Sample Clauses

Complement in animal studies. Animal models have been useful in testing hypotheses of asthma pathogenesis. Studies in murine models have suggested the involvement of C3a and C5a in the development of allergic asthma (Xxxxx et al. 2003). Xxxxx et al found the inhibition of complement activation decreases airway inflammation and hyperresponsiveness in mice (Xxxxx et al. 2003). Reports from some laboratories including those of Xxxxxx et al have documented the importance of complement activation, the C3a anaphylatoxin, and its receptor, C3aR, in promoting Th2 effector functions in a mouse model of bronchopulmonary allergy (Xxxxxx et al. 2006). Xxxxxx et al found that all features of the experimental allergic asthma model are either abrogated or severely reduced in the genetic absence of the C3aR (Xxxxxx et al. 2002). These results suggest that ligands of C3aR may make a major contribution to allergic lung disease. Xxxxxx and coworkers showed C3aR-deficient mice were protected against AHR, and showed decreased Th2-cell responses, including reduced IL-4 production (Xxxxxx et al. 2001a). Further still, in another study involving challenge of antigen-sensitised animals, C3 deficient mice showed diminished AHR, lung eosinophil infiltration and IL-4 production as well as reduced Ag- specific IgE and IgG1 responses, clearly demonstrating that these features of asthma are significantly attenuated in the absence of C3 (Xxxxxx et al. 2002). These data provide compelling evidence that C3a and C3aR have the propensity to mediate much of the pulmonary inflammation observed in the acute sensitisation/aerosol situation and suggest that C3a on binding C3aR may play a significant role in bridging innate and adaptive Th2 immune responses in asthma (Xxxxxx et al. 2002). The role of C5 in asthma remains controversial. Xxxx et al examined the contribution of C5 in mice at three critical checkpoints during the course of disease- those being a) initiation of airway inflammation, b) maintenance of AHR, and c) sustainment of an ongoing airway response to allergen provocation (Xxxx et al. 2005). Their results indicate that C5 is probably activated intrapulmonarily after infections or exposure to allergen and that C5 inhibition has profound effects at all three critical checkpoints (Xxxx et al. 2005). Xxxxxx et al’s data suggest that C5a plays an important protective role in allergic lung disease by suppressing inflammatory responses and Th2 effector functions observed in their experimental model. There is a suggest...