Allergens Induce Enhanced Bronchoconstriction and Leukotriene Production in C5 Deficient Mice
Bolgos, Gerald L.
Remick, Daniel G.
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CitationMcKinley, Laura, Jiyoun Kim, Gerald L Bolgos, Javed Siddiqui, Daniel G Remick. "Allergens induce enhanced bronchoconstriction and leukotriene production in C5 deficient mice" Respiratory Research 7(1):129. (2006)
BACKGROUND. Previous genetic analysis has shown that a deletion in the complement component 5 gene-coding region renders mice more susceptible to allergen-induced airway hyperresponsiveness (AHR) due to reduced IL-12 production. We investigated the role of complement in a murine model of asthma-like pulmonary inflammation. METHODS. In order to evaluate the role of complement B10 mice either sufficient or deficient in C5 were studied. Both groups of mice immunized and challenged with a house dust extract (HDE) containing high levels of cockroach allergens. Airways hyper-reactivity was determined with whole-body plesthysmography. Bronchoalveolar lavage (BAL) was performed to determine pulmonary cellular recruitment and measure inflammatory mediators. Lung homogenates were assayed for mediators and plasma levels of IgE determined. Pulmonary histology was also evaluated. RESULTS. C5-deficient mice showed enhanced AHR to methylcholine challenge, 474% and 91% increase above baseline Penh in C5-deficient and C5-sufficient mice respectively, p < 0.001. IL-12 levels in the lung homogenate (LH) were only slightly reduced and BAL IL-12 was comparable in C5-sufficient and C5-deficient mice. However, C5-deficient mice had significantly higher cysteinyl-leukotriene levels in the BAL fluid, 1913 +/- 246 pg/ml in C5d and 756 +/- 232 pg/ml in C5-sufficient, p = 0.003. CONCLUSION. These data demonstrate that C5-deficient mice show enhanced AHR due to increased production of cysteinyl-leukotrienes.