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Activation of type II alveolar epithelial cells during acute endotoxemia.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2002 Apr; Vol. 282 (4), pp. L872-80. - Publication Year :
- 2002
-
Abstract
- Lung injury induced by acute endotoxemia is associated with increased generation of inflammatory mediators such as nitric oxide and eicosanoids, which have been implicated in the pathophysiological process. Although production of these mediators by alveolar macrophages (AM) has been characterized, the response of type II cells is unknown and was assessed in the present studies. Acute endotoxemia caused a rapid (within 1 h) and prolonged (up to 48 h) induction of nitric oxide synthase-2 (NOS-2) in type II cells but a delayed response in AM (12-24 h). In both cell types, this was associated with increased nitric oxide production. Although type II cells, and to a lesser extent AM, constitutively expressed cyclooxygenase-2, acute endotoxemia did not alter this activity. Endotoxin administration had no effect on mitogen-activated protein kinase or protein kinase B-alpha (PKB-alpha) expression. However, increases in phosphoinositide 3-kinase and phospho-PKB-alpha were observed in type II cells. The finding that this was delayed for 12-24 h suggests that these proteins do not play a significant role in the regulation of NOS-2 in this model. After endotoxin administration to rats, a rapid (within 1-2 h) activation of nuclear factor-kappaB was observed. This response was transient in type II cells but was sustained in AM. Interferon regulatory factor-1 (IRF-1) was also activated rapidly in type II cells. In contrast, IRF-1 activation was delayed in AM. These data demonstrate that type II cells, like AM, are highly responsive during acute endotoxemia and may contribute to pulmonary inflammation.
- Subjects :
- Acute Disease
Animals
Cyclooxygenase 2
DNA-Binding Proteins metabolism
Endotoxemia immunology
Epithelial Cells enzymology
Epithelial Cells immunology
Female
Interferon Regulatory Factor-1
Isoenzymes metabolism
Macrophages, Alveolar immunology
NF-kappa B antagonists & inhibitors
NF-kappa B metabolism
Nitric Oxide metabolism
Nitric Oxide Synthase metabolism
Nitric Oxide Synthase Type II
Phosphoproteins metabolism
Prostaglandin-Endoperoxide Synthases metabolism
Protein Binding physiology
Pulmonary Alveoli cytology
Pulmonary Alveoli immunology
Rats
Rats, Sprague-Dawley
Respiratory Mucosa cytology
Respiratory Mucosa immunology
Specific Pathogen-Free Organisms
Endotoxemia metabolism
Pulmonary Alveoli enzymology
Respiratory Mucosa enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1040-0605
- Volume :
- 282
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 11880315
- Full Text :
- https://doi.org/10.1152/ajplung.00217.2001