Corticosteroid-resistant asthma is associated with classical antimicrobial activation of airway macrophages Elena Goleva, PhD, Pia J. Hauk, MD, Clifton.

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Presentation transcript:

Corticosteroid-resistant asthma is associated with classical antimicrobial activation of airway macrophages Elena Goleva, PhD, Pia J. Hauk, MD, Clifton F. Hall, MSc, Andrew H. Liu, MD, David W.H. Riches, PhD, Richard J. Martin, MD, Donald Y.M. Leung, MD, PhD Journal of Allergy and Clinical Immunology Volume 122, Issue 3, Pages 550-559.e3 (September 2008) DOI: 10.1016/j.jaci.2008.07.007 Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Significant increase in expression of markers associated with classical macrophage activation in BAL cells from subjects with CR asthma compared with subjects with CS asthma, as shown by means of real-time PCR. GAPDH, Glyceraldehyde-3-phosphate dehydrogenase. Journal of Allergy and Clinical Immunology 2008 122, 550-559.e3DOI: (10.1016/j.jaci.2008.07.007) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Expression of markers of alternative macrophage activation in BAL cells from subjects with CR asthma compared with those from subjects with CS asthma, as shown by means of real-time PCR. SOCS1, Suppressor of cytokine signaling 1. Journal of Allergy and Clinical Immunology 2008 122, 550-559.e3DOI: (10.1016/j.jaci.2008.07.007) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Increased expression of proinflammatory cytokines in the BAL fluid samples from subjects with CR asthma compared with those from subjects with CS asthma, as detected by using the 17-plex panel ELISA (n = 6 for the CR asthma group [open bars], n = 4 for the CS asthma group [solid bars]). Expression of 17 different targets was analyzed in 100 μL of BAL fluid and normalized to the total protein amount in each sample. MCP-1, Monocyte chemoattractant protein 1; MIP-1β, macrophage inflammatory protein 1β. Journal of Allergy and Clinical Immunology 2008 122, 550-559.e3DOI: (10.1016/j.jaci.2008.07.007) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Presence of high amounts of LPS in BAL fluid from subjects with CR asthma. A, The content of LPS in BAL fluid was analyzed by using the chromogenic LAL test and normalized to the total protein level in each sample. IL-8 mRNA expression by BAL cells from subjects with CR asthma and subjects with CS asthma positively correlates with the percentage of neutrophils in BAL samples (B) and amounts of LPS in BAL fluid (C; solid circles, subjects with CR asthma; open circles, subjects with CS asthma). Journal of Allergy and Clinical Immunology 2008 122, 550-559.e3DOI: (10.1016/j.jaci.2008.07.007) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 LPS induces functional steroid resistance in normal human monocytes in vitro. Monocytes were cultured with 10 ng/mL LPS for 1 or 24 hours before addition of dexamethasone for an additional 24 hours. IL-6 (A and B) and TNF-α (C and D) levels were measured in cell-culture supernatants by means of ELISA (n = 6). Journal of Allergy and Clinical Immunology 2008 122, 550-559.e3DOI: (10.1016/j.jaci.2008.07.007) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions