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

Sandra Grumelli,David B Corry,Remzi Bag,Li-Zhen Song,Linda Green,Joseph Huh,Joan Hacken,Farrah Kheradmand,Dorothy E Lewis,Ling Song,Rafael Espada,Peter J Barnes

doi:10.1371/journal.pmed.0010008

Abstract

ABSTRACTBackgroundChronic 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 FindingsWe 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.ConclusionsThese 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.

Highlights

Chronic inhalation of tobacco smoke causes progressive lung destruction in susceptible individuals, resulting in chronic obstructive pulmonary disease (COPD) and emphysema, two well-described clinical syndromes with poorly understood pathogenesis [1,2,3]
We found that loss of lung function in patients with chronic obstructive pulmonary disease and emphysema was associated with a high percentage of CD4þ and CD8þ T lymphocytes that expressed chemokine receptors CCR5 and CXCR3, but not CCR3 or CCR4
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

Summary

Introduction

Chronic inhalation of tobacco smoke causes progressive lung destruction in susceptible individuals, resulting in chronic obstructive pulmonary disease (COPD) and emphysema, two well-described clinical syndromes with poorly understood pathogenesis [1,2,3]. A potential role for T cells in COPD has been suggested in several recent studies that show CD8þ T cells are increased in the lungs of people who smoke [8,9,10,11]. Airway limitation, another characteristic of human asthma, is clinically linked to an accelerated rate of loss of lung function in smoker individuals [13]. It has been suggested, that asthma and COPD may involve the same type of recruited inflammatory cells, differing only in their location within the lung [14]. The researchers showed that the immune cells could tell other lung cells to produce chemicals that can damage the lung

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Conclusion