Role of eosinophil chemotactic factor by T lymphocytes on airway hyperresponsiveness in a murine model of allergic asthma.
Airway hyperresponsiveness (AHR) is an important feature of bronchial asthma. Although the incidence of AHR has genetic and environmental components, the mechanism of AHR in asthma remains unclear. The identification of genes that are preferentially expressed in a murine model of AHR could help elucidate the molecular mechanisms of this pulmonary pathology. Suppressive subtractive hybridization analysis revealed that eosinophil chemotactic factor by T lymphocytes (ECF-L), a mouse chitinase family protein, was selectively expressed in the lungs of mice with AHR. Induction of ECF-L expression was observed soon after allergen exposure but before the onset of airway inflammation. Cell-specific ECF-L expression was examined by in situ hybridization using digoxigenin-labeled antisense RNA probes and immunofluorescence staining. The assay revealed that the ECF-L-expressing cells in the lungs of the AHR-model mice are alveolar macrophages. Intratracheal administration of an adenoviral vector that expressed antisense ECF-L RNA (Ad-ECF-L-AS) suppressed AHR and eosinophil infiltration. These results indicate that ECF-L may play a critical role in allergic inflammation and bronchial asthma.
Iwashita
Hiroki
H
Pharmacology Research Laboratory II, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 10 Wadai, Tsukuba, Ibaraki, 300-4293, Japan. Iwashita_Hiroki@takeda.co.jp
Morita
Shigeru
S
Sagiya
Yoji
Y
Nakanishi
Atsushi
A
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D002631:Chemotactic Factors, Eosinophil / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D008168:Lung / Q000166:cytology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016372:RNA, Antisense / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014132:Trachea / Q000378:metabolism
D018925:Chemokines; D002631:Chemotactic Factors, Eosinophil; D016372:RNA, Antisense; D012333:RNA, Messenger; C482719:eosinophil chemotactic factor-L, mouse