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Kinetics of apoptosis in the lung of mice with allergic airway inflammation
Author(s) -
Taku Kodama,
Tomohiro Matsuyama,
Seiko Miyata,
H Nishimura,
Yasuhiro Nishioka,
O Kitada,
Minoru Sugita
Publication year - 1998
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.1998.00374.x
Subject(s) - tunel assay , apoptosis , eosinophil , terminal deoxynucleotidyl transferase , ovalbumin , immunology , dna fragmentation , lung , inflammation , pathology , biology , bronchoalveolar lavage , medicine , immune system , programmed cell death , asthma , biochemistry
Background Apoptosis has been suggested as a means to facilitate the resolution of eosinophilic inflammation in bronchial asthma. However, the natural course of apoptosis has not been elucidated in vivo , and there is no direct evidence for eosinophilic apoptosis within lung tissue. Objective The purpose of this study is to clarify whether the apoptosis occurs within the lung tissue, and to define the time‐course of change in apoptosis ratio during the resolution of pulmonary eosinophilic inflammation. Methods Ovalbumin (OVA)‐sensitized Balb/c mice were challenged with aerosolized OVA. We studied apoptotic cells in the lung of OVA‐sensitized mice at 1, 3, 7 and 14 days after OVA challenge by in situ detection of DNA fragmentation with deoxynucleotidyl transferase deoxyuridyl triphosphatase nick endlabelling (TUNEL) technique. Apoptotic cells also were identified by electron microscopic analysis in the lung 7 days after OVA challenge. Results The TUNEL‐method revealed that eosinophils localized in the subepithelium of bronchi undergo apoptosis following OVA challenge. Electron microscopy confirmed the presence of apoptotic cells, apoptotic bodies, and macrophages ingesting apoptotic bodies within the lung tissue. The number of apoptotic cells increased concomitantly with the increase in eosinophilic infiltration for 3 days post‐challenge. However, both the apoptotic cell counts and the apoptotic ratio continued to increase even after the eosinophil count peaked, indicating rather late induction of apoptosis in the lung. In addition, TUNEL‐positive cells were localized in the lung for 14 days post‐challenge, indicating prolonged induction of apoptosis after the OVA challenge. Conclusion Our findings constitute direct evidence of eosinophilic apoptosis in situ , and display the kinetics of apoptosis in the lung of the allergic inflammation.