Murine Model of Chronic Respiratory Inflammation
The respiratory mucosa is exposed to the external environment each time we breathe and therefore requires a robust and sophisticated immune defense system. As with other mucosal sites, the respiratory mucosal immune system must balance its response to pathogens while also regulating inflammatory immune cell-mediated tissue damage. In the airways, a failure to tightly control immune responses to a pathogen can result in chronic inflammation and tissue destruction with an overzealous response being deleterious for the host. Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death in the US and both the prevalence of and mortality rate of this disease is increasing annually. COPD is characterized by intermittent disease exacerbation. The causal contribution of bacterial infections to exacerbations of COPD is now widely accepted, accounting for at least 50% of all exacerbations. Non-typeable Haemophilus influenzae and Moraxella catarrhalis (both gram-negative bacteria) along with Streptococcus pneumoniae (a gram-positive bacterium) are the three most common bacterial pathogens that cause respiratory tract infections in COPD patients. The colonization of bacteria in the lower airways is similar to a low-grade smoldering infection that induces chronic airway inflammation. Chronic low-grade infection can induce a persistent inflammatory response in the airways and parenchyma. Inefficient removal of bacteria from the lower respiratory tract is characteristic of chronic bronchitis. Inflammation is believed to be central to the pathogenesis of exacerbations, but a clear understanding of the inflammatory changes during an exacerbation of COPD has yet to emerge. As bacterial colonization of the lung in COPD patients is a chronic inflammatory condition highlighted by frequent bouts of exacerbation and clearance, we sought to reproduce this chronic pathogen-mediated inflammation in a murine model by repeatedly delivering the intact, whole, live bacteria intra-tracheally to the lungs.
KeywordsChronic Obstructive Pulmonary Disease Respiratory Syncytial Virus Chronic Obstructive Pulmonary Disease Patient Alveolar Macrophage Chronic Obstructive Pulmonary Disease Exacerbation
This work was supported by a grant from NIH AI069379 to Yasmin Thanavala.
- 11.National Heart, Lung and Blood Institute (1998) Morbidity and mortality chartbook on cardiovascular, lung and blood diseases. National Institutes of Health, 1998 Bethesda, MDGoogle Scholar
- 19.Shizu M, Itoh Y, Sunahara R, Chujo S, Hayashi H, Ide Y, Takii T, Koshiko M, Chung SW, Hayakawa K, Miyazawa K, Hirose K, Onozaki K (2008) Cigarette smoke condensate upregulates the gene and protein expression of pro-inflammatory cytokines in human fibroblast-like synoviocyte line. J Interferon Cytokine Res 28:509–521PubMedCrossRefGoogle Scholar
- 45.Heguy A, O’Connor TP, Luettich K, Worgall S, Cieciuch A, Harvey BG, Hackett NR, Crystal RG (2006) Gene expression profiling of human alveolar macrophages of phenotypically normal smokers and nonsmokers reveals a previously unrecognized subset of genes modulated by cigarette smoking. J Mol Med 84:318–328PubMedCrossRefGoogle Scholar
- 62.Seemungal T, Harper-Owen R, Bhowmik A, Moric I, Sanderson G, Message S, MacCallum P, Meade TW, Jeffries DJ, Johnston SL, Wedzicha JA (2001) Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 164:1618–1623PubMedGoogle Scholar
- 63.Centers for Disease Control (2004) Updated interim influenza vaccination recommendations: 2004–05 influenza season. http://www.cdc.gov/flu. Accessed 31 Dec 2004
- 64.Advisory Committee of Immunization Practices (2005) Prevention and control of influenza: recommendations of the advisory committee of immunization practices. MMWR 54:1–40Google Scholar