Long-term intratracheal lipopolysaccharide exposure in mice results in chronic lung inflammation and persistent pathology.
Lipopolysaccharide (LPS), a major proinflammatory glycolipid component of the gram-negative bacterial cell wall, is one of the agents ubiquitously present as contaminant on airborne particles, including air pollution, organic dusts, and cigarette smoke. Chronic exposure to significant levels of LPS is reported to be associated with the development and/or progression of many types of lung diseases, including asthma, chronic bronchitis, and progressive irreversible airflow obstruction, that are all characterized by chronic inflammatory processes in the lung. In the present study, pathologic effects of long-term LPS exposure to the lung were investigated in detail. To this end, a murine model in which mice were exposed to repeated intratracheal instillation of Escherichia coli LPS was developed. We show that long-term LPS instillation in mice results in persistent chronic pulmonary inflammation, characterized by peribronchial and perivascular lymphocytic aggregates (CD4(+), CD8(+), and CD19(+)), parenchymal accumulation of macrophages and CD8(+) T cells, and altered cytokine expression. Furthermore, airway and alveolar alterations such as mucus cell metaplasia, airway wall thickening, and irreversible alveolar enlargement accompanied the chronic inflammatory response. Interestingly, the observed inflammatory and pathologic changes mimic changes observed in human subjects with chronic inflammatory lung diseases, especially chronic obstructive pulmonary disease (COPD), suggesting that this murine model could be applicable to dissect the role of inflammation in the pathogenesis of these disease conditions.
Vernooy
Juanita H J
JH
Department of Pulmonology, Maastricht University, Maastricht, The Netherlands.
Dentener
Mieke A
MA
van Suylen
Robert J
RJ
Buurman
Wim A
WA
Wouters
Emiel F M
EF
D000818:Animals; D018941:Antigens, CD19 / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004926:Escherichia coli / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D009092:Mucous Membrane / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014132:Trachea / Q000378:metabolism*
D018941:Antigens, CD19; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger