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This Article Full Text Full Text (PDF) All Versions of this Article: 293/2/L383    most recent 00024.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Elizur, A. Articles by Senior, R. M. Search for Related Content PubMed PubMed Citation Articles by Elizur, A. Articles by Senior, R. M.

Clara cells impact the pulmonary innate immune response to LPS

¹Division of Allergy and Pulmonary Medicine, Department of Pediatrics, and ²Division of Pulmonary and Critical Care Medicine, Department of Medicine, and ⁴Department of Cell Biology and Physiology, Washington University School of Medicine, and ³Department of Pathology, St. Louis University Health Science Center, St. Louis, Missouri

Submitted 18 January 2007 ; accepted in final form 21 May 2007

Airway epithelial cells secrete proinflammatory mediators in response to LPS, but cytokine production by a prominent nonciliated bronchiolar epithelial cell, the Clara cell, specifically, is unknown. To investigate Clara cell cytokine production in response to LPS, we used a transformed murine Clara cell line, C22, and isolated Clara cells from C57Bl/6 mice. Stimulation of both cell types with LPS resulted in significant upregulation of keratinocyte-derived chemokine (KC) and monocyte chemoattractant protein-1, but did not induce TNF- production. To determine whether LPS induces cytokine production by Clara cells in vivo, LPS was instilled intratracheally into mice. KC was expressed by Clara cells, alveolar type 2 cells, and alveolar macrophages, 2 h after LPS administration, as determined by in situ hybridization. TNF-, although not expressed in airway epithelial cells, was expressed primarily in alveolar macrophages in response to LPS. To assess the impact of Clara cells on KC and TNF- production in the lung in the early response to LPS, mice were treated with naphthalene to selectively induce Clara cell injury before LPS stimulation. KC expression in the airways and the lung periphery, and KC and TNF- levels in the bronchoalveolar lavage fluid, were significantly reduced in naphthalene-treated vs. vehicle-treated mice after LPS stimulation. Furthermore, transwell cocultures of C22 cells and RAW264.7 macrophages indicated that C22 cells released a soluble factor(s) in response to LPS that enhanced macrophage production of TNF-. These results indicate that Clara cells elaborate cytokines and modulate the lung innate immune response to LPS.

airway; cytokines; epithelium; inflammation; lung

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