The development of emphysema is thought to be due to an imbalance of proteases (especially neutrophil elastase [NE]) and antiproteases with loosening of the respiratory epithelium as an early event. We investigated the effect of NE on respiratory epithelial cell adherence in vitro , in the presence of varying concentrations and combinations of native inhibitors, alpha-1-proteinase inhibitor (PI) and secretory leukoprotease inhibitor (SLPI). SLPI was two to 12 times more effective than PI at preventing the effects of NE, especially when enzyme:inhibitor ratios were almost equivalent. Even when the concentration of SLPI was only 10% of the total (as in normal peripheral lung secretions), it gave greater protection than PI alone. This suggests that SLPI plays an important role in controlling neutrophil elastaseinduced inflammation and tissue damage.

Annals of the New York Academy of SciencesVolume 624, Issue 1 p. 358-358 The Blotchy Mouse, Lung Desmosine, and Emphysema T. D. TETLEY, T. D. TETLEY Departments of Medicine and Histopathology Charing Cross & Westminster Medical School London, UKSearch for more papers by this authorG. J. PHILLIPS, G. J. PHILLIPS Departments of Medicine and Histopathology Charing Cross & Westminster Medical School London, UKSearch for more papers by this authorA. GUZ, A. GUZ Departments of Medicine and Histopathology Charing Cross & Westminster Medical School London, UKSearch for more papers by this authorB. FOX, B. FOX Departments of Medicine and Histopathology Charing Cross & Westminster Medical School London, UKSearch for more papers by this author T. D. TETLEY, T. D. TETLEY Departments of Medicine and Histopathology Charing Cross & Westminster Medical School London, UKSearch for more papers by this authorG. J. PHILLIPS, G. J. PHILLIPS Departments of Medicine and Histopathology Charing Cross & Westminster Medical School London, UKSearch for more papers by this authorA. GUZ, A. GUZ Departments of Medicine and Histopathology Charing Cross & Westminster Medical School London, UKSearch for more papers by this authorB. FOX, B. FOX Departments of Medicine and Histopathology Charing Cross & Westminster Medical School London, UKSearch for more papers by this author First published: May 1991 https://doi.org/10.1111/j.1749-6632.1991.tb17048.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume624, Issue1Pulmonary Emphysema: The Rationale for Therapeutic InterventionMay 1991Pages 358-358 RelatedInformation

Annals of the New York Academy of SciencesVolume 624, Issue 1 p. 328-328 Bronchial Inhibitor in Human Lung B. FOX, B. FOX Department of Histopathology Charing Cross & Westminster Medical School London, UKSearch for more papers by this authorT. B. BULL, T. B. BULL Department of Anatomy Charing Cross & Westminster Medical School London, UKSearch for more papers by this authorA. GUZ, A. GUZ Department of Medicine Charing Cross & Westminster Medical School London, UKSearch for more papers by this authorT. D. TETLEY, T. D. TETLEY Department of Medicine Charing Cross & Westminster Medical School London, UKSearch for more papers by this author B. FOX, B. FOX Department of Histopathology Charing Cross & Westminster Medical School London, UKSearch for more papers by this authorT. B. BULL, T. B. BULL Department of Anatomy Charing Cross & Westminster Medical School London, UKSearch for more papers by this authorA. GUZ, A. GUZ Department of Medicine Charing Cross & Westminster Medical School London, UKSearch for more papers by this authorT. D. TETLEY, T. D. TETLEY Department of Medicine Charing Cross & Westminster Medical School London, UKSearch for more papers by this author First published: May 1991 https://doi.org/10.1111/j.1749-6632.1991.tb17035.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume624, Issue1Pulmonary Emphysema: The Rationale for Therapeutic InterventionMay 1991Pages 328-328 RelatedInformation

Conference Abstract| January 01 1990 Do Human Alveolar Type II Cells Proliferate “In Vitro”? L Bingle; L Bingle 1Department of Medicine and Histopathology, Charing Cross and Westminster Medical School, Fulham Palace Road, London, W6 8RF Search for other works by this author on: This Site PubMed Google Scholar TB Bull; TB Bull 1Department of Medicine and Histopathology, Charing Cross and Westminster Medical School, Fulham Palace Road, London, W6 8RF Search for other works by this author on: This Site PubMed Google Scholar B Fox; B Fox 1Department of Medicine and Histopathology, Charing Cross and Westminster Medical School, Fulham Palace Road, London, W6 8RF Search for other works by this author on: This Site PubMed Google Scholar A Guz; A Guz *Department of Biochemistry, University of Wales, PO Box 903, Cardiff, CF1 1ST. Search for other works by this author on: This Site PubMed Google Scholar RJ Richards; RJ Richards 1Department of Medicine and Histopathology, Charing Cross and Westminster Medical School, Fulham Palace Road, London, W6 8RF Search for other works by this author on: This Site PubMed Google Scholar TD Tetley TD Tetley 1Department of Medicine and Histopathology, Charing Cross and Westminster Medical School, Fulham Palace Road, London, W6 8RF Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Online ISSN: 1470-8736 Print ISSN: 0143-5221 © 1990 The Biochemical Society and the Medical Research Society1990 Clin Sci (Lond) (1990) 78 (s22): 3P–4P. https://doi.org/10.1042/cs078003Pc Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation L Bingle, TB Bull, B Fox, A Guz, RJ Richards, TD Tetley; Do Human Alveolar Type II Cells Proliferate “In Vitro”?. Clin Sci (Lond) 1 January 1990; 78 (s22): 3P–4P. doi: https://doi.org/10.1042/cs078003Pc Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1990 The Biochemical Society and the Medical Research Society1990 Article PDF first page preview Close Modal You do not currently have access to this content.

Alveolar Type II epithelial cells dedifferentiate rapidly in vitro. Studies with animal tissue suggest that cell-cell and extracellular matrix-cell interactions are important in the retention of Type II cell morphology in vitro. Thus, in this study with human tissue, alveolar Type II cells, alveolar macrophages, and spindle cells were prepared from the same sample of lung (obtained following lobectomy for cancer, n = 3), cocultured on glass cover slips or tissue culture plastic, and studied by light microscopy with scanning (SEM) and transmission (TEM) electron microscopy for 8 days. The primary cell isolates contained approximately 45% Type II cells; the remainder were macrophages or unidentifiable cells. Clusters, made up of a single layer of cuboidal Type II cells around a central core of connective tissue (largely collagen and some elastic tissue), formed above a monolayer of spindle cells. The Type II cells were morphologically similar to those seen in vivo. The cells were still cuboidal at 8 days but had lost their lamellar bodies, which were released into the medium via the apical surface. The clusters increased in size with time (area, microns 2: day 1, 29(5-143) x 10(2); day 8, 63(10-311) x 10(2); mean(range); p less than 0.02) without changing in number per culture, suggesting Type II cell proliferation. This may have been due to factors produced by the other cells and adherence to the extracellular matrix (ECM); (free collagen fibers, present in the original preparation, spindle cells, and/or Type II cells could be responsible for presence of ECM). We propose this as a useful model for the study of human Type II epithelial cells in vitro.

To test the role of elastase in the pathogenesis of emphysema human neutrophil elastase (HNE) was localised by electron microscopy using an immunogold staining technique. Specific localisation of HNE to elastic tissue in emphysema did not occur, but non-specific binding of immunoglobulin G (IgG) to elastic tissue in emphysematous and normal lung tissue, which was completely blocked by the non-immune serum that was homologous to the gold labelled second antibody, was found. HNE was also present, however, in the granules of neutrophils in the same sections. Non-specific labelling associated with elastin was probably due to binding of IgG to the high numbers of hydrophobic and charged regions known to be present in this molecule, and it is concluded that our findings do not support the existence of high concentrations of elastase in association with elastin in emphysematous lung tissue.

The aim of this study was to overcome difficulties of assessing the true incidence of electromicroscopic abnormalities of microtubular structure of cilia by examining large numbers of cilia from each case. The effects of different fixatives on the appearances of cilia were also studied. Bronchial biopsies were examined from 35 subjects who were being investigated for various lung diseases and nasal biopsies from 12 subjects (7 with retinitis pigmentosa (R.P.), and 5 healthy controls). Numerous pieces of normal looking bronchial wall from a lobectomy specimen were used to examine the effect of six different fixatives. 2.9% of bronchial cilia (mean of 890 cilia examined) and 2.4% of nasal cilia (mean of 808 cilia examined) showed microtubular abnormalities. Examining large numbers of cilia established that increased microtubular abnormalities were associated with smoking, chronic pulmonary infection and carcinoma of the lung. There was a significant increase (p less than 0.001) in microtubular abnormalities in nasal cilia in R.P. The appearances of cilia varied considerably with different fixatives. The numbers of dynein arms seen and the ease of recognising radial spokes and microtubules was particularly effected by fixation. The true incidence of microtubular abnormalities can only be ascertained by examining large numbers of cilia.

An unlabelled antibody peroxidase-antiperoxidase method for the detection of IgG, IgM, complement (C3 and Clq), fibrinogen and albumin was applied to routinely processed paraffin sections of lung from 27 cases. The results in 11 cases were compared with those obtained by immunofluorescence using frozen sections. Tissue was obtained from surgical specimens of cases with interstitial pneumonia comprising 10 of the usual type (UIP) and three of the desquamative type (DIP). Tissue was also obtained from the specimens of cases with sarcoidosis (two cases) and granulomatous inflammation of unknown cause (one case). There were 11 control cases, nine with primary carcinoma of the lung and two with metastatic tumours of the lung. Immunoglobulins of various types and complement were seen in diseased lung tissue. Although most of these deposits were probably due to a non-immunological mechanism there was evidence of the possible implication of immune complexes in three cases of UIP and in the interstitial pneumonia present in the two cases of sarcoidosis. The immunoperoxidase technique is a more sensitive method than immunofluorescence and has the additional advantage of the easy identification of the precise sites of the various deposits.