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Respiratory Research

, 6:147

First Online: 16 December 2005Received: 07 July 2005Accepted: 16 December 2005


BackgroundChronic obstructive pulmonary disease is associated with a chronic inflammatory response of the host to chronic exposure to inhaled toxic gases and particles. Although inflammatory cells of both the innate and adaptive immune system infiltrate the lungs in pulmonary emphysema and form lymphoid follicles around the small airways, the exact role of the acquired immune system in the pathogenesis of emphysema is not known.

MethodsIn this study, wild type Balb-c mice and immunodeficient scid mice – which lack functional B- and T-cells – were exposed to mainstream cigarette smoke CS for 5 weeks or 6 months.

ResultsSubacute CS-exposure for 5 weeks significantly increased innate inflammatory cells neutrophils, macrophages and dendritic cells in the bronchoalveolar lavage BAL fluid of wild type mice and scid mice, which correlated with the CS-induced upregulation of the chemokines Monocyte Chemotactic Protein-1, Macrophage Inflammatory Protein-3α and KC = mouse Interleukin-8. Chronic CS-exposure for 6 months significantly increased the number of neutrophils, macrophages, dendritic cells, CD4 and CD8 T-lymphocytes in BAL fluid and lungs of wild type mice compared to air-exposed littermates, and augmented the size and number of peribronchial lymphoid follicles. In contrast, neither B-lymphocytes, nor T-lymphocytes, nor lymphoid follicles could be discerned in the lungs of air- or CS-exposed scid mice. Importantly, chronic CS-exposure induced pulmonary emphysema in both wild type animals and scid mice, as evidenced by a significant increase in the mean linear intercept and the destructive index of CS-exposed versus air-exposed animals. The CS-induced emphysema was associated with increased mRNA expression of matrix metalloproteinase-12 in the lungs and increased protein levels of Tumor Necrosis Factor-α in the BAL fluid of CS-exposed Balb-c and scid mice compared to air-exposed littermates.

ConclusionThis study suggests that the adaptive immune system is not required per se to develop pulmonary emphysema in response to chronic CS-exposure, since emphysema can be induced in scid mice, which lack lymphoid follicles as well as functional B- and T-cells.

AbbreviationsBALbronchoalveolar lavage

COPDchronic obstructive pulmonary disease

CScigarette smoke

DIdestructive index

GOLDGlobal initiative for chronic Obstructive Lung Disease

Lm:mean linear intercept

MCP-1Monocyte Chemotactic Protein-1 CCL2

MIP-3αMacrophage Inflammatory Protein-3α CCL20

MMP-12matrix metalloproteinase-12

N.S.not significant

scid:severe combined immunodeficiency

TNF-αTumor Necrosis Factor-α

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Autor: An I D-hulst - Tania Maes - Ken R Bracke - Ingel K Demedts - Kurt G Tournoy - Guy F Joos - Guy G Brusselle


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