RAGE processing in chronic airway conditions: Involvement of Staphylococcus aureus and ECP Koen Van Crombruggen, PhD, Gabriele Holtappels, Natalie De.

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Presentation transcript:

RAGE processing in chronic airway conditions: Involvement of Staphylococcus aureus and ECP Koen Van Crombruggen, PhD, Gabriele Holtappels, Natalie De Ruyck, Lara Derycke, PhD, Peter Tomassen, MD, Claus Bachert, MD, PhD Journal of Allergy and Clinical Immunology Volume 129, Issue 6, Pages 1515-1521.e8 (June 2012) DOI: 10.1016/j.jaci.2012.02.021 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Quantification of tissue sRAGE (A) and mRAGE (B) protein levels by means of ELISA in controls and CRSsNP and CRSwNP patients. Values are expressed as pg/g tissue and presented as box-and-whisker plots showing the minimum and maximum values, the lower and upper quartiles, the median (as a line), and the mean (as a cross). **P < .01; ***P < .001. Journal of Allergy and Clinical Immunology 2012 129, 1515-1521.e8DOI: (10.1016/j.jaci.2012.02.021) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Immunolabeling with antibodies directed against RAGE in human sinonasal tissues from controls (A), CRSsNP patients (B), and CRSwNP patients (C) (magnification ×200). Journal of Allergy and Clinical Immunology 2012 129, 1515-1521.e8DOI: (10.1016/j.jaci.2012.02.021) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Effect of S aureus on tissue sRAGE ex vivo (n = 8): under baseline conditions, sRAGE was not detectable in tissue-cube supernatants. The presence of S aureus resulted in a clear-cut increase in the levels of endogenous sRAGE in the supernatants, while the levels of sRAGE in the tissue-cube pellets were reduced by S aureus. ∗P < .05; ∗∗∗P < .001. Journal of Allergy and Clinical Immunology 2012 129, 1515-1521.e8DOI: (10.1016/j.jaci.2012.02.021) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 sRAGE protein levels in relation to IL-5–negative versus IL-5–positive tissues (A) or ECP-low versus ECP-high tissues (B). Values are presented as box-and-whisker plots showing the minimum and maximum values, the lower and upper quartiles, the median (as a line), and the mean (as a cross). *P < .05; **P < .01; ***P < .001. Journal of Allergy and Clinical Immunology 2012 129, 1515-1521.e8DOI: (10.1016/j.jaci.2012.02.021) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 ECP, but not IL-5, induced the breakdown of recombinant sRAGE in vitro (n = 5). **P < .01. Journal of Allergy and Clinical Immunology 2012 129, 1515-1521.e8DOI: (10.1016/j.jaci.2012.02.021) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Quantification of tissue MMP-3 (A), MMP-7 (B), MMP-9 (C), and ADAM-10 (D) protein levels by means of ELISA in controls and CRSsNP and CRSwNP patients. Values are expressed as pg/g tissue and presented as box-and-whisker plots showing the minimum and maximum values, the lower and upper quartiles, the median (as a line), and the mean (as a cross). **P < .01; ***P < .001. Journal of Allergy and Clinical Immunology 2012 129, 1515-1521.e8DOI: (10.1016/j.jaci.2012.02.021) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 mRAGE (A) and esRAGE (B) mRNA expression by means of RT-PCR in the tissue of controls and CRSsNP and CRSwNP patients. Data are expressed as normalized relative copy number and presented as box-and-whisker plots showing the minimum and maximum values, the lower and upper quartiles, the median (as a line), and the mean (as a cross). *P < .05; **P < .01. Journal of Allergy and Clinical Immunology 2012 129, 1515-1521.e8DOI: (10.1016/j.jaci.2012.02.021) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Inverse correlation of mRAGE levels in the tissue of controls with the level of MMP-9 (A) (rs = −0.8200; P = .002) and the level of ADAM-10 (B) (rs = −0.6818; P = .0208). Journal of Allergy and Clinical Immunology 2012 129, 1515-1521.e8DOI: (10.1016/j.jaci.2012.02.021) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Tissue levels of ECP in IL-5–negative and IL-5–positive samples over all patient groups (A) and in the separate clinical entities (B). Values are expressed as pg/g tissue and presented as box-and-whisker plots showing the minimum and maximum values, the lower and upper quartiles, the median (as a line), and the mean (as a cross). **P < .01; ***P < .001. Journal of Allergy and Clinical Immunology 2012 129, 1515-1521.e8DOI: (10.1016/j.jaci.2012.02.021) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 Effect of recombinant 5 μg/mL sRAGE on the release of IL-1β, TNF-α, and IL-5 proteins in an ex vivo human tissue assay (n = 6). *P < .05. Journal of Allergy and Clinical Immunology 2012 129, 1515-1521.e8DOI: (10.1016/j.jaci.2012.02.021) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions