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An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema

BACKGROUND: Chronic obstructive pulmonary disease and emphysema are a frequent result of long-term smoking, but the exact mechanisms, specifically which types of cells are associated with the lung destruction, are unclear. METHODS AND FINDINGS: We studied different subsets of lymphocytes taken from...

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Autores principales: Grumelli, Sandra, Corry, David B, Song, Li-Zhen, Song, Ling, Green, Linda, Huh, Joseph, Hacken, Joan, Espada, Rafael, Bag, Remzi, Lewis, Dorothy E, Kheradmand, Farrah
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC523885/
https://www.ncbi.nlm.nih.gov/pubmed/15526056
http://dx.doi.org/10.1371/journal.pmed.0010008
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author Grumelli, Sandra
Corry, David B
Song, Li-Zhen
Song, Ling
Green, Linda
Huh, Joseph
Hacken, Joan
Espada, Rafael
Bag, Remzi
Lewis, Dorothy E
Kheradmand, Farrah
author_facet Grumelli, Sandra
Corry, David B
Song, Li-Zhen
Song, Ling
Green, Linda
Huh, Joseph
Hacken, Joan
Espada, Rafael
Bag, Remzi
Lewis, Dorothy E
Kheradmand, Farrah
author_sort Grumelli, Sandra
collection PubMed
description BACKGROUND: Chronic obstructive pulmonary disease and emphysema are a frequent result of long-term smoking, but the exact mechanisms, specifically which types of cells are associated with the lung destruction, are unclear. METHODS AND FINDINGS: We studied different subsets of lymphocytes taken from portions of human lungs removed surgically to find out which lymphocytes were the most frequent, which cell-surface markers these lymphocytes expressed, and whether the lymphocytes secreted any specific factors that could be associated with disease. We found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a high percentage of CD4(+) and CD8(+) T lymphocytes that expressed chemokine receptors CCR5 and CXCR3 (both markers of T helper 1 cells), but not CCR3 or CCR4 (markers of T helper 2 cells). Lung lymphocytes in patients with chronic obstructive pulmonary disease and emphysema secrete more interferon gamma—often associated with T helper 1 cells—and interferon-inducible protein 10 and monokine induced by interferon, both of which bind to CXCR3 and are involved in attracting T helper 1 cells. In response to interferon-inducible protein 10 and monokine induced by interferon, but not interferon gamma, lung macrophages secreted macrophage metalloelastase (matrix metalloproteinase-12), a potent elastin-degrading enzyme that causes tissue destruction and which has been linked to emphysema. CONCLUSIONS: These data suggest that Th1 lymphoctytes in the lungs of people with smoking-related damage drive progression of emphysema through CXCR3 ligands, interferon-inducible protein 10, and monokine induced by interferon.
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spelling pubmed-5238852004-11-02 An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema Grumelli, Sandra Corry, David B Song, Li-Zhen Song, Ling Green, Linda Huh, Joseph Hacken, Joan Espada, Rafael Bag, Remzi Lewis, Dorothy E Kheradmand, Farrah PLoS Med Research Article BACKGROUND: Chronic obstructive pulmonary disease and emphysema are a frequent result of long-term smoking, but the exact mechanisms, specifically which types of cells are associated with the lung destruction, are unclear. METHODS AND FINDINGS: We studied different subsets of lymphocytes taken from portions of human lungs removed surgically to find out which lymphocytes were the most frequent, which cell-surface markers these lymphocytes expressed, and whether the lymphocytes secreted any specific factors that could be associated with disease. We found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a high percentage of CD4(+) and CD8(+) T lymphocytes that expressed chemokine receptors CCR5 and CXCR3 (both markers of T helper 1 cells), but not CCR3 or CCR4 (markers of T helper 2 cells). Lung lymphocytes in patients with chronic obstructive pulmonary disease and emphysema secrete more interferon gamma—often associated with T helper 1 cells—and interferon-inducible protein 10 and monokine induced by interferon, both of which bind to CXCR3 and are involved in attracting T helper 1 cells. In response to interferon-inducible protein 10 and monokine induced by interferon, but not interferon gamma, lung macrophages secreted macrophage metalloelastase (matrix metalloproteinase-12), a potent elastin-degrading enzyme that causes tissue destruction and which has been linked to emphysema. CONCLUSIONS: These data suggest that Th1 lymphoctytes in the lungs of people with smoking-related damage drive progression of emphysema through CXCR3 ligands, interferon-inducible protein 10, and monokine induced by interferon. Public Library of Science 2004-10 2004-10-19 /pmc/articles/PMC523885/ /pubmed/15526056 http://dx.doi.org/10.1371/journal.pmed.0010008 Text en Copyright: © 2004 Grumelli et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Grumelli, Sandra
Corry, David B
Song, Li-Zhen
Song, Ling
Green, Linda
Huh, Joseph
Hacken, Joan
Espada, Rafael
Bag, Remzi
Lewis, Dorothy E
Kheradmand, Farrah
An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema
title An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema
title_full An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema
title_fullStr An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema
title_full_unstemmed An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema
title_short An Immune Basis for Lung Parenchymal Destruction in Chronic Obstructive Pulmonary Disease and Emphysema
title_sort immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC523885/
https://www.ncbi.nlm.nih.gov/pubmed/15526056
http://dx.doi.org/10.1371/journal.pmed.0010008
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