Role of CCL21 and CCL19 in allergic inflammation in the ovalbumin-specific murine asthmatic model - 17/08/11
, Hiroyuki Tashimo, MD, PhD b, Yukiko Matsuo a, b, Hirofumi Ishida, MD, PhD b, Kenta Yoshiura, MD a, Katsuaki Sato, PhD c, Naohide Yamashita, MD, PhD d, Terutaka Kakiuchi, MD, PhD e, Ken Ohta, MD, PhD b
Reprint requests: Naomi Yamashita, MD, PhD, Department of Pharmacology, Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi Nishitokyo-shi, Tokyo 202-8585 Japan.Tokyo and Yokohama, Japan
Abstract |
Background |
Dendritic cells are the most powerful of the antigen-presenting cells and are known to play important roles in sensitization and inflammation in allergen-specific asthma. Various cytokines and chemokines are involved in the maturation and activation of dendritic cells. Among them is CC chemokine ligand (CCL)21, a key chemokine in the entry of naive T cells and antigen-stimulated dendritic cells into the T-cell zones of secondary lymphoid organs, which is a critical process in antigen-specific T-cell activation.
Objective |
We studied the role of CCL21 in airway inflammation in asthma by using BALB/c-plt/plt (plt) mice, which possess genetic defects in expression of both CCL21 and CCL19.
Methods |
Plt and control BALB/c mice were immunized with ovalbumin and alum 4 times and thereafter were subjected to a 2-week regimen of ovalbumin inhalation.
Results |
In plt mice, ovalbumin-specific IgE response was delayed compared with control BALB/c mice, but they had the same level of response after final immunization. Although airway inflammation and response to acetylcholine were significantly reduced compared with BALB/c mice, significant eosinophilic inflammation and hyperresponsiveness were also observed in plt mice after 2 weeks of inhalation. Four weeks after cessation of inhalation, airway inflammation and hyperresponsiveness in plt mice were greater than in BALB/c mice. At the time of resolution of airway inflammation, IL-10 production was enhanced in BALB/c mice but not in plt mice.
Conclusion |
The chemokines CCL21 and CCL19 were critical for resolution of airway inflammation.
Clinical implications |
The findings about the chemokines for induction and resolution of inflammation are key to establishing a new strategy for asthma immunotherapy.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, airway hyperresponsiveness, CCL21, dendritic cells, airway inflammation
Abbreviations used : APC, BALF, CCL, CCR, DC, PAS, Penh, plt
Plan
| Supported in part by grants-in-aid for Scientific Research and by a High-Tech Research Center grant from the Ministry of Education, Culture, Sports, Science and Technology (#15590828 to Naomi Yamashita and #13670473 to Musashino University). Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 117 - N° 5
P. 1040-1046 - mai 2006 Retour au numéro
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