Importance of myeloid dendritic cells in persistent airway disease after repeated allergen exposure.

Abstract

RATIONALE:

There is conflicting information about the development and resolution of airway inflammation and airway hyperresponsiveness (AHR) after repeated airway exposure to allergen in sensitized mice.

METHODS:

Sensitized BALB/c and C57BL/6 mice were exposed to repeated allergen challenge on 3, 7, or 11 occasions. Airway function in response to inhaled methacholine was monitored; bronchoalveolar lavage fluid inflammatory cells were counted; and goblet cell metaplasia, peribronchial fibrosis, and smooth muscle hypertrophy were quantitated on tissue sections. Bone marrow-derived dendritic cells were generated after differentiation of bone marrow cells in the presence of growth factors.

RESULTS:

Sensitization to ovalbumin (OVA) in alum, followed by three airway exposures to OVA, induced lung eosinophilia, goblet cell metaplasia, mild peribronchial fibrosis, and peribronchial smooth muscle hypertrophy; increased levels of interleukin (IL)-4, IL-5, IL-13, granulocyte-macrophage colony-stimulating factor, transforming growth factor-beta(1), eotaxin-1, RANTES (regulated on activation, normal T-cell expressed and secreted), and OVA-specific IgG1 and IgE; and resulted in AHR. After seven airway challenges, development of AHR was markedly decreased as was the production of IL-4, IL-5, and IL-13. Levels of IL-10 in both strains and the level of IL-12 in BALB/c mice increased. After 11 challenges, airway eosinophilia and peribronchial fibrosis further declined and the cytokine and chemokine profiles continued to change. At this time point, the number of myeloid dendritic cells and expression of CD80 and CD86 in lungs were decreased compared with three challenges. After 11 challenges, intratracheal instillation of bone marrow-derived dendritic cells restored AHR and airway eosinophilia.

CONCLUSIONS:

These data suggest that repeated allergen exposure leads to progressive decreases in AHR and allergic inflammation, through decreases in myeloid dendritic cell numbers.

• Authors: Toshiyuki Koya, Taku Kodama, Katsuyuki Takeda, Nobuaki Miyahara, Eun-Seok Yang, Christian Taube, Anthony Joetham, Jung-Won Park, Azzeddine Dakhama, Erwin W Gelfand
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 173 Issue 1 Pg. 42-55 (Jan 01 2006) ISSN: 1073-449X [Print] United States
• PMID: 16192450 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Allergens
• Ovalbumin

Topics

• Allergens (immunology)
• Animals
• Bone Marrow Cells
• Bronchial Hyperreactivity (immunology)
• Bronchoalveolar Lavage Fluid (immunology)
• Cells, Cultured
• Dendritic Cells (immunology)
• Disease Models, Animal
• Female
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Ovalbumin (immunology)