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Formation and Neutrophil Sequestration into the Murine Lungs1
*
Unité de Pharmacologie Cellulaire, Unité Associée IP/Institut National de la Santé et de la Recherche Médicale (INSERM) 485, and
Unité d’Histopathologie, Institut Pasteur, Paris, France; and
Commissariat à l’Energie Atomique (CEA), Service de Pharmacologie et d’Immunologie, CEA Saclay, Gif sur Yvette, France
Bronchopulmonary hyperreactivity (BHR), an increased responsiveness
to nonspecific bronchoconstrictor agents, is a well-known
characteristic of bronchial asthma. It has been recently suggested that
the severity of this disease is related to the endotoxin content of
house dust. In the present report, it is shown that the i.p.
administration of bacterial LPS to mice is followed by a marked early
dose-dependent BHR in response to methacholine. The microscopic
examination showed no ultrastructural lesions of the lungs or of the
airways, but a marked neutrophil accumulation in the capillaries, as
confirmed by an increase of the lung content in the neutrophil enzyme
marker myeloperoxidase. In parallel, high levels of TNF-
were found
in plasma as well as its transcripts in the lung tissues. Using
immunologic (anti-TNF- and anti-granulocyte Abs), and
pharmacologic (dexamethasone and vinblastine) tools, it is demonstrated
that BHR is apparently neither related to the presence of neutrophils
in the pulmonary microvasculature nor to the synthesis of TNF-.
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