Article

Effects of Respiratory Syncytial Virus Infection on Dendritic Cells and Cysteinyl Leukotrienes in Lung Tissues of a Murine Model of Asthma

Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Allergology International 07/2007; 56(2):165-9. DOI: 10.2332/allergolint.O-06-476
Source: PubMed

ABSTRACT Pulmonary dendritic cells (DCs) play critical roles in both allergy and in viral infection. Levels of cysteinyl leukotrienes (cysLTs) increase after allergen sensitization and viral infection and can modulate the migration and functions of DCs. The present study examines the effects of respiratory syncytial virus (RSV) infection on numbers of DCs and cysLT concentrations in lung tissues of mice sensitized with mite allergen.
We examined Control, Dermatophagoides farinae allergen sensitized (Df), RSV infected (RSV) and Df allergen sensitized and RSV infected (Df-RSV) Balb/c mice. We then determined the number of CD11c-positive DCs and the LT concentration in lung tissues of the mice and examined lung pathology and cytokine profiles in thoracic lymph nodes.
Infection with RSV significantly enhanced allergic airway inflammation in Df mice with concomitant increases in Th1 and Th2 immunity. The number of DCs and the cysLT concentrations were significantly increased in the lungs of Df and RSV mice and more so in Df-RSV, than in Df mice.
The present findings suggest that RSV infection increases the number of DCs and the cysLT concentrations in lung tissues of asthma patients, both of which could result in enhanced allergic airway inflammation.

0 Followers
 · 
104 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Asthma and allergic rhinitis frequently coexist in the same patient. There is a similarity and variation as well as potential relationship between asthma and allergic rhinitis. There is an increasing evidence to suggest a major involvement of airway epithelial cells in the pathogenesis of asthma and allergic rhinitis. The present review describes the importance of the airway epithelial cell in the development of allergic airway diseases, its role as the primary airway defense against exposure of the airway and lung to inflammatory stimuli and antigens and as an important player through activation of epithelial Toll-like receptors (TLRs) to provide an important link between innate immunity and allergic disease. Additionally, airway epithelial cells can act as inflammatory promoters capable of directing dendritic cells (DCs) towards a T helper 2 (Th2) response, and as active producers of several inflammatory/anti-inflammatory mediators. It is hypothesized that airway epithelial cells may play as both inflammatory initiator and immuno-pathological feedback regulation between allergic rhinitis and asthma via release of systemic inflammatory mediators. Thus, airway epithelial cells may be valuable therapeutic targets for discovery and development of new drugs and/or new therapeutic strategies to treat asthma and allergic rhinitis.
    Respiratory Medicine 08/2008; 102(7):949-55. DOI:10.1016/j.rmed.2008.01.017 · 2.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Respiratory syncytial virus (RSV) is an important cause of viral respiratory disease in children, and RSV bronchiolitis has been associated with the development of asthma in childhood. RSV spreads from the eye and nose to the human respiratory tract. Correlative studies of humans and direct infection studies of BALB/c mice have established the eye as a significant pathway of entry of RSV to the lung. At the same time, RSV infection of the eye produces symptoms resembling allergic conjunctivitis. Cysteinyl leukotrienes (CysLTs) are known promoters of allergy and inflammation, and the first step in their biogenesis from arachidonic acid is catalyzed by 5-lipoxygenase (5-LO) in concert with the 5-LO-activating protein (FLAP). We have recently developed a novel compound, AM679, which is a topically applied and potent inhibitor of FLAP. Here we show with the BALB/c mouse eye RSV infection model that AM679 markedly reduced the RSV-driven ocular pathology as well as the synthesis of CysLTs in the eye. In addition, AM679 decreased the production of the Th2 cell cytokine interleukin-4 but did not increase the viral load in the eye or the lung. These results suggest that FLAP inhibitors may be therapeutic for RSV-driven eye disease and possibly other inflammatory eye indications.
    Clinical and vaccine Immunology: CVI 09/2009; 16(11):1654-9. DOI:10.1128/CVI.00220-09 · 2.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Synthesis of regulated on activation, normal T-cells expressed and secreted (RANTES) in the airway has previously been shown to be elevated after respiratory syncytial virus (RSV) infection. However, since few studies have examined whether RSV-infected asthma patients express a higher level of RANTES than do normal individuals, we used a murine model of asthma to address this question. We prepared Dermatophagoides farinae-sensitized mice as an asthma model, and then infected them with RSV and analyzed the changes in airway responsiveness and the cell populations and cytokine levels of bronchoalveolar lavage fluid. RANTES synthesis increased in response to RSV infection in both control mice and in asthma model (D. farinae) mice. However, there was no significant difference in the amount of RANTES produced following RSV infection between control and D. farinae mice. RSV infection affected neither interferon-γsynthesis nor airway responsiveness in either control or D. farinae mice. RSV infection did not induce more RANTES in a murine model of asthma than in control mice.
    Korean Journal of Pediatrics 11/2011; 54(11):456-62. DOI:10.3345/kjp.2011.54.11.456
Show more

Preview

Download
2 Downloads
Available from