Corticosteroid Suppression of Lipoxin A\(_4\) and Leukotriene B\(_4\) from Alveolar Macrophages in Severe Asthma
Bhavsar, Pankaj K
Hew, Mark J
Pfeffer, Michael A
Chung, Kian Fan
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CitationBhavsar, Pankaj K., Bruce D. Levy, Mark J. Hew, Michael A. Pfeffer, Shamsah Kazani, Elliot Israel, and Kian Fan Chung. 2010. Corticosteroid suppression of lipoxin A\(_4\) and leukotriene B\(_4\) from alveolar macrophages in severe asthma. Respiratory Research 11(1): 71.
AbstractBackground: An imbalance in the generation of pro-inflammatory leukotrienes, and counter-regulatory lipoxins is present in severe asthma. We measured leukotriene B\(_4\) (LTB\(_4\)), and lipoxin A\(_4\) (LXA\(_4\)) production by alveolar macrophages (AMs) and studied the impact of corticosteroids. Methods: AMs obtained by fiberoptic bronchoscopy from 14 non-asthmatics, 12 non-severe and 11 severe asthmatics were stimulated with lipopolysaccharide (LPS,10 \(\mu\)g/ml) with or without dexamethasone (10-6M). LTB\(_4\) and LXA\(_4\) were measured by enzyme immunoassay. Results: LXA\(_4\) biosynthesis was decreased from severe asthma AMs compared to non-severe (p < 0.05) and normal subjects (p < 0.001). LXA\(_4\) induced by LPS was highest in normal subjects and lowest in severe asthmatics (p < 0.01). Basal levels of LTB\(_4\) were decreased in severe asthmatics compared to normal subjects (p < 0.05), but not to non-severe asthma. LPS-induced LTB\(_4\) was increased in severe asthma compared to non-severe asthma (p < 0.05). Dexamethasone inhibited LPS-induced LTB\(_4\) and LXA\(_4\), with lesser suppression of LTB\(_4\) in severe asthma patients (p < 0.05). There was a significant correlation between LPS-induced LXA\(_4\) and FEV\(_1\) (% predicted) (r\(_s\) = 0.60; < 0.01). Conclusions: Decreased LXA\(_4\) and increased LTB4 generation plus impaired corticosteroid sensitivity of LPS-induced LTB\(_4\) but not of LXA\(_4\) support a role for AMs in establishing a pro-inflammatory balance in severe asthma.
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