Striking deposition of toxic eosinophil major basic protein in mucus: Implications for chronic rhinosinusitis Jens U. Ponikau, MD, David A. Sherris,

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Presentation transcript:

Striking deposition of toxic eosinophil major basic protein in mucus: Implications for chronic rhinosinusitis Jens U. Ponikau, MD, David A. Sherris, MD, Gail M. Kephart, BS, Eugene B. Kern, MD, David J. Congdon, MD, Cheryl R. Adolphson, MS, Margaret J. Springett, BS, Gerald J. Gleich, MD, Hirohito Kita, MD Journal of Allergy and Clinical Immunology Volume 116, Issue 2, Pages 362-369 (August 2005) DOI: 10.1016/j.jaci.2005.03.049 Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 Photomicrographs of CRS specimens stained for MBP by means of immunofluorescence or stained with hematoxylin and eosin. Panel a demonstrates eosinophilic inflammation in tissue, eosinophil clusters (black arrows) in mucus, subepithelial basement membrane thickening, and damaged epithelium (yellow arrows) (hematoxylin and eosin counterstain of Panel b; original magnification, 160×). Panel b shows MBP in tissue is contained within the cells or in intact granules (punctate staining) outside the cells. In mucus, diffuse MBP staining is in eosinophil clusters (white arrows) and outside of clusters (anti-MBP; original magnification, 160×). Panel c shows minimal tissue eosinophilia, massive eosinophilia in mucus, subepithelial basement membrane thickening, and the damaged epithelium (yellow arrows) (hematoxylin and eosin; original magnification, 400×). Panel d (serial section of Panel c) shows few intact eosinophils in tissue, intense diffuse MBP deposition within the mucus, and MBP adjacent to the epithelial surface (anti-MBP; original magnification, 400×). Panels e (tissue) and f (mucus) show intact eosinophils (white arrows) and free granules (punctate staining, blue arrows); diffuse extracellular MBP staining (orange arrows) appears unique to mucus (anti-MBP; original magnification, 1400×). Serial sections stained with normal rabbit IgG were negative (results not shown). Journal of Allergy and Clinical Immunology 2005 116, 362-369DOI: (10.1016/j.jaci.2005.03.049) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 Comparisons of eosinophilic and neutrophilic inflammation in tissue versus mucus. The graphs show the mean MBP and elastase immunofluorescence scores for intact eosinophils and neutrophils, punctate staining (MBP and elastase within intact extracellular granules), and diffuse staining (extracellular MBP and elastase not in granules) in tissue and mucus from 22 patients with CRS. Each dot represents the mean score of 3 independent examiners for each patient (scoring on vertical axis follows the grading system presented in the Methods section). Panel a shows a CRS specimen stained with anti-MBP; note the abundant diffuse MBP in mucus that is absent in tissue. Panel b shows a CRS specimen stained with anti-elastase; note the virtual absence of diffuse elastase in both mucus and tissue (original magnification, 400×). Journal of Allergy and Clinical Immunology 2005 116, 362-369DOI: (10.1016/j.jaci.2005.03.049) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 Comparison of digitized areas of minimal and maximal MBP or elastase staining in the tissue and mucus of patients with CRS. To demonstrate the heterogenicity within the 22 specimens, these data points represent the minimal and maximal percentages of area positive for MBP or elastase immunofluorescence. The horizontal lines show the median values in each group. Journal of Allergy and Clinical Immunology 2005 116, 362-369DOI: (10.1016/j.jaci.2005.03.049) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 4 Transmission electron micrographs of sinus tissue from a patient with CRS. Panel a shows the characteristic electron-dense secondary granules within an intact cell (white arrows) and intact extracellular granules in the tissue (black arrows; original magnification, 10,000×). Panel b shows immunogold labeling (black dots) for MBP and demonstrates that MBP is localized within the intact granules; note the lack of MBP labeling in the surrounding tissue (original magnification, 33,000×). Journal of Allergy and Clinical Immunology 2005 116, 362-369DOI: (10.1016/j.jaci.2005.03.049) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 5 MBP concentrations in mucus specimens from patients with CRS and healthy control subjects. Mucus specimens were extracted with 0.15 M NaCl, and MBP was measured in the supernatants by means of RIA. MBP was detected in the maxillary sinus mucus and in the nasal cavity mucus of patients with CRS but not in mucus from the healthy control subjects. Horizontal bars indicate mean values for each group. Journal of Allergy and Clinical Immunology 2005 116, 362-369DOI: (10.1016/j.jaci.2005.03.049) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions