Abstract
T lymphocytes and eosinophils are important components of the inflammatory cell infiltrate in bronchial mucosa in asthma. Because activated lymphocytes migrate through the thoracic duct and the general circulation to remote glandular and mucosal sites, we initiated this study to evaluate pathological abnormalities and immunoreactivity for interleukin (IL) 3, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF) of intestinal mucosa in bronchial asthma. 15 asthmatic patients, 8 nonasthmatic patients with chronic obstructive pulmonary disease, 6 atopic nonasthmatic healthy controls, and 6 nonatopic healthy controls were studied. Duodenal biopsies were performed by endoscopy. A significantly increased number of intraepithelial lymphocytes and eosinophils and a significant accumulation of mononuclear cells (lymphocytes and mast cells) and eosinophils in the lamina propria were detected in asthmatics and atopic controls. Immunostaining with antibodies directed against IL-3, IL-5, and GM-CSF was positive in asthmatics and atopic controls, whereas no staining was observed in nonatopic controls and chronic obstructive pulmonary disease. Combined ultrastructural study and immunogold labeling demonstrated that IL-3, IL-5, and GM-CSF were localized in eosinophils and mast cells. Although devoid of gastrointestinal symptoms, asthmatics and asymptomatic atopics had duodenal pathological abnormalities mimicking those observed in the bronchial mucosa in asthma, suggesting that the whole mucosal immune system is involved in bronchial asthma.
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- Azzawi M., Bradley B., Jeffery P. K., Frew A. J., Wardlaw A. J., Knowles G., Assoufi B., Collins J. V., Durham S., Kay A. B. Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1407–1413. doi: 10.1164/ajrccm/142.6_Pt_1.1407. [DOI] [PubMed] [Google Scholar]
- Beasley R., Roche W. R., Roberts J. A., Holgate S. T. Cellular events in the bronchi in mild asthma and after bronchial provocation. Am Rev Respir Dis. 1989 Mar;139(3):806–817. doi: 10.1164/ajrccm/139.3.806. [DOI] [PubMed] [Google Scholar]
- Berman J. S. Lymphocytes in the lung: should we continue to exalt only BALT? Am J Respir Cell Mol Biol. 1990 Aug;3(2):101–102. doi: 10.1165/ajrcmb/3.2.101. [DOI] [PubMed] [Google Scholar]
- Bienenstock J., Befus D., McDermott M., Mirski S., Rosenthal K. Regulation of lymphoblast traffic and localization in mucosal tissues, with emphasis on IgA. Fed Proc. 1983 Dec;42(15):3213–3217. [PubMed] [Google Scholar]
- Bousquet J., Chanez P., Lacoste J. Y., Barnéon G., Ghavanian N., Enander I., Venge P., Ahlstedt S., Simony-Lafontaine J., Godard P. Eosinophilic inflammation in asthma. N Engl J Med. 1990 Oct 11;323(15):1033–1039. doi: 10.1056/NEJM199010113231505. [DOI] [PubMed] [Google Scholar]
- Bradding P., Roberts J. A., Britten K. M., Montefort S., Djukanovic R., Mueller R., Heusser C. H., Howarth P. H., Holgate S. T. Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol. 1994 May;10(5):471–480. doi: 10.1165/ajrcmb.10.5.8179909. [DOI] [PubMed] [Google Scholar]
- Brandtzaeg P., Baklien K. Immunohistochemical studies of the formation and epithelial transport of immunoglobulins in normal and diseased human intestinal mucosa. Scand J Gastroenterol Suppl. 1976;36:1–45. [PubMed] [Google Scholar]
- Broide D. H., Paine M. M., Firestein G. S. Eosinophils express interleukin 5 and granulocyte macrophage-colony-stimulating factor mRNA at sites of allergic inflammation in asthmatics. J Clin Invest. 1992 Oct;90(4):1414–1424. doi: 10.1172/JCI116008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coffman R. L., Shrader B., Carty J., Mosmann T. R., Bond M. W. A mouse T cell product that preferentially enhances IgA production. I. Biologic characterization. J Immunol. 1987 Dec 1;139(11):3685–3690. [PubMed] [Google Scholar]
- Colombel J. F., Torpier G., Janin A., Klein O., Cortot A., Capron M. Activated eosinophils in adult coeliac disease: evidence for a local release of major basic protein. Gut. 1992 Sep;33(9):1190–1194. doi: 10.1136/gut.33.9.1190. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Desreumaux P., Janin A., Colombel J. F., Prin L., Plumas J., Emilie D., Torpier G., Capron A., Capron M. Interleukin 5 messenger RNA expression by eosinophils in the intestinal mucosa of patients with coeliac disease. J Exp Med. 1992 Jan 1;175(1):293–296. doi: 10.1084/jem.175.1.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Djukanović R., Roche W. R., Wilson J. W., Beasley C. R., Twentyman O. P., Howarth R. H., Holgate S. T. Mucosal inflammation in asthma. Am Rev Respir Dis. 1990 Aug;142(2):434–457. doi: 10.1164/ajrccm/142.2.434. [DOI] [PubMed] [Google Scholar]
- Frew A. J., Kay A. B. The relationship between infiltrating CD4+ lymphocytes, activated eosinophils, and the magnitude of the allergen-induced late phase cutaneous reaction in man. J Immunol. 1988 Dec 15;141(12):4158–4164. [PubMed] [Google Scholar]
- Hamid Q., Azzawi M., Ying S., Moqbel R., Wardlaw A. J., Corrigan C. J., Bradley B., Durham S. R., Collins J. V., Jeffery P. K. Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J Clin Invest. 1991 May;87(5):1541–1546. doi: 10.1172/JCI115166. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kita H., Ohnishi T., Okubo Y., Weiler D., Abrams J. S., Gleich G. J. Granulocyte/macrophage colony-stimulating factor and interleukin 3 release from human peripheral blood eosinophils and neutrophils. J Exp Med. 1991 Sep 1;174(3):745–748. doi: 10.1084/jem.174.3.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Korn E. R., Foroozan P. Endoscopic biopsies of normal duodenal mucosa. Gastrointest Endosc. 1974 Nov;21(2):51–54. doi: 10.1016/s0016-5107(74)73790-7. [DOI] [PubMed] [Google Scholar]
- Marsh M. N. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue'). Gastroenterology. 1992 Jan;102(1):330–354. [PubMed] [Google Scholar]
- Mestecky J., McGhee J. R., Michalek S. M., Arnold R. R., Crago S. S., Babb J. L. Concept of the local and common mucosal immune response. Adv Exp Med Biol. 1978;107:185–192. doi: 10.1007/978-1-4684-3369-2_22. [DOI] [PubMed] [Google Scholar]
- Moqbel R., Hamid Q., Ying S., Barkans J., Hartnell A., Tsicopoulos A., Wardlaw A. J., Kay A. B. Expression of mRNA and immunoreactivity for the granulocyte/macrophage colony-stimulating factor in activated human eosinophils. J Exp Med. 1991 Sep 1;174(3):749–752. doi: 10.1084/jem.174.3.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rudzik R., Clancy R. L., Perey D. Y., Day R. P., Bienenstock J. Repopulation with IgA-containing cells of bronchial and intestinal lamina propria after transfer of homologous Peyer's patch and bronchial lymphocytes. J Immunol. 1975 May;114(5):1599–1604. [PubMed] [Google Scholar]
- Sedgwick J. D., Holt P. G. Induction of IgE-isotype specific tolerance by passive antigenic stimulation of the respiratory mucosa. Immunology. 1983 Dec;50(4):625–630. [PMC free article] [PubMed] [Google Scholar]
- Sedgwick J. D., Holt P. G. Induction of IgE-secreting cells and IgE isotype-specific suppressor T cells in the respiratory lymph nodes of rats in response to antigen inhalation. Cell Immunol. 1985 Aug;94(1):182–194. doi: 10.1016/0008-8749(85)90095-4. [DOI] [PubMed] [Google Scholar]
- Wallaert B., Janin A., Lassalle P., Copin M. C., Devisme L., Gosset P., Gosselin B., Tonnel A. B. Airway-like inflammation of minor salivary gland in bronchial asthma. Am J Respir Crit Care Med. 1994 Sep;150(3):802–809. doi: 10.1164/ajrccm.150.3.8087355. [DOI] [PubMed] [Google Scholar]
- Wallen N., Kita H., Weiler D., Gleich G. J. Glucocorticoids inhibit cytokine-mediated eosinophil survival. J Immunol. 1991 Nov 15;147(10):3490–3495. [PubMed] [Google Scholar]
- Wodnar-Filipowicz A., Heusser C. H., Moroni C. Production of the haemopoietic growth factors GM-CSF and interleukin-3 by mast cells in response to IgE receptor-mediated activation. Nature. 1989 May 11;339(6220):150–152. doi: 10.1038/339150a0. [DOI] [PubMed] [Google Scholar]