Laura Fregonese, MD, Fiona J

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Expression of the anaphylatoxin receptors C3aR and C5aR is increased in fatal asthma Laura Fregonese, MD, Fiona J. Swan, BSc, Annemarie van Schadewijk, BSc, Marisa Dolhnikoff, MD, PhD, Mario A. Santos, MD, PhD, Mohamed R. Daha, PhD, Jan Stolk, MD, PhD, Thomas Tschernig, MD, PhD, Peter J. Sterk, MD, PhD, Pieter S. Hiemstra, PhD, Klaus F. Rabe, MD, PhD, Thais Mauad, MD, PhD Journal of Allergy and Clinical Immunology Volume 115, Issue 6, Pages 1148-1154 (June 2005) DOI: 10.1016/j.jaci.2005.01.068 Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 C3aR expression in large airways of a control patient (CTRL; A, B), a patient with FA (C, D), and a patient with MIA (E, F). A, Bronchial wall of a CTRL subject, with no staining of the submucosal vessels (arrows). B, Submucosal vessel in detail. C, Bronchial wall of a subject with FA, with intense staining of the submucosal vessels (arrows) and the epithelium. D, Submucosal vessel in detail. E, Bronchial biopsy of a subject with MIA, with weak or absent staining in the submucosal vessels (arrow). The epithelium is negative. F, Submucosal vessel in detail. E, Epithelium; M, myeloid cells; N, nucleus; Sm, smooth muscle layer; Sr, subepithelial reticular layer; Sv, submucosal vessels. The white squares in the left panels indicate the areas magnified in the right panels. Original magnification, 400×. Journal of Allergy and Clinical Immunology 2005 115, 1148-1154DOI: (10.1016/j.jaci.2005.01.068) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 C3aR expression in parenchymal tissue from a control subject (CTRL; A, B) and FA (C, D). A, CTRL subject with weak or absent staining in the parenchymal vessels (small vessels and capillaries; arrows). B, Vessel in detail. C, Diffuse and intense staining in the parenchymal vessels in FA (arrows). Mild edema of the alveolar septa is present. D, Vessel in detail. N, Nucleus; M, myeloid cells; Pv, parenchymal vessels. The white squares in the left panels indicate the areas magnified in the right panels. Original magnification, 400×. Journal of Allergy and Clinical Immunology 2005 115, 1148-1154DOI: (10.1016/j.jaci.2005.01.068) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 Box-whisker plots of C3aR in submucosal vessels of control (CTRL), MIA, and FA subjects (A) and in parenchymal vessels of CTRL and FA subjects (B). Journal of Allergy and Clinical Immunology 2005 115, 1148-1154DOI: (10.1016/j.jaci.2005.01.068) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 4 C5aR in large airways from control (CTRL; A, B) and FA (C, D) subjects, and in biopsies from MIA (E, F). A, Bronchial wall of a CTRL subject, with positive inflammatory cells infiltrating the submucosal and the epithelial layer (arrows). B, A detail of the epithelial layer, showing weakly positive granular staining. C, Bronchial wall of a FA subject, with intense epithelial staining for C5aR. Positive myeloid cells infiltrate the submucosal and epithelial layer (arrows). D, A detail of the epithelial layer, showing intense granular staining (arrows). E, Bronchial biopsy of a MIA subject, with positive myeloid cells infiltrating the submucosal and epithelial layer (arrows), and moderate epithelial staining. F, A detail of the epithelial layer. C, Cilia; E, epithelium; M, myeloid cells; N, nucleus; Sm, smooth muscle layer; Sr, subepithelial reticular layer. The white squares in the left panels indicate the areas magnified in the right panels. Original magnification, 400×. Journal of Allergy and Clinical Immunology 2005 115, 1148-1154DOI: (10.1016/j.jaci.2005.01.068) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 5 Box-whisker plots of C5aR in epithelium from large airways of controls (CTRL), MIA, and FA. Journal of Allergy and Clinical Immunology 2005 115, 1148-1154DOI: (10.1016/j.jaci.2005.01.068) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions