Activation of type II alveolar epithelial cells during acute endotoxemia

American Journal of Physiology - Lung Cellular and Molecular Physiology - Tập 282 Số 4 - Trang L872-L880 - 2002
Vasanthi R. Sunil1, Agnieszka J. Connor1, Yan Guo1, Jeffrey D. Laskin1, Debra L. Laskin1
1Department of Toxicology and Pharmacology, Rutgers University and Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-8020

Tóm tắt

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-α (PKB-α) expression. However, increases in phosphoinositide 3-kinase and phospho-PKB-α 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-κB 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.

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American Journal of Physiology - Lung Cellular and Molecular Physiology

Tập 282 Số 4

L872-L880

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