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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-04-1102. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-04-1102v1 100/12/4193    most recent 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 PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Berclaz, P.-Y. Articles by Trapnell, B. C. Search for Related Content PubMed PubMed Citation Articles by Berclaz, P.-Y. Articles by Trapnell, B. C. Related Collections Phagocytes Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2002, Vol. 100, No. 12, pp. 4193-4200 PHAGOCYTES GM-CSF, via PU.1, regulates alveolar macrophage FcR-mediated phagocytosis and the IL-18/IFN--mediated molecular connection between innate and adaptive immunity in the lung Pierre-Yves Berclaz, Yoko Shibata, Jeffrey A. Whitsett, and Bruce C. Trapnell From Children's Hospital Medical Center, Cincinnati, OH. Severely impaired pulmonary microbial clearance was observed in granulocyte-macrophage colony-stimulating factor (GM-CSF)-deficient mice. To determine mechanisms by which GM-CSF mediates lung host defense, FcR-mediated phagocytosis (opsonophagocytosis) by alveolar macrophages (AMs) was assessed in GM-CSF-sufficient (GM+/+) and -deficient (GM/) mice and in GM/ mice expressing GM-CSF only in the lungs from a surfactant protein C (SPC) promoter (SPC-GM+/+/GM/). Opsonophagocytosis by GM/ AMs was severely impaired and was restored by pulmonary GM-CSF expression in vivo or by PU.1 expression in vitro. Defective opsonophagocytosis by GM/ AMs was associated with decreased FcR expression. Because interferon- (IFN-) augments macrophage FcR levels, the role of GM-CSF/PU.1 in the regulation of AM FcR expression by IFN- was assessed during adenoviral lung infection. Adenoviral infection stimulated IFN- production and augmented FcR levels on AMs in GM-CSF-expressing but not GM/ mice. However, IFN- exposure ex vivo stimulated FcR expression on GM/ AMs. Because interleukin-18 (IL-18) and IL-12 stimulate IFN- production during adenoviral infection, their role in GM-CSF/PU.1 regulation of IFN--augmented FcR expression on AMs was assessed. Adenoviral infection stimulated IL-18 and IL-12 production in GM-CSF-expressing mice, but both were markedly reduced or absent in GM/ mice. IL-18 expression by GM/ AMs was severely impaired and was restored by pulmonary GM-CSF expression in vivo or by PU.1 expression in vitro. Pulmonary administration of IL-18 in GM/ mice stimulated IFN- production and restored FcR expression on AMs. These results show that GM-CSF, via PU.1, regulates constitutive AM FcR expression and opsonophagocytosis and is required for the IFN--dependent regulation of AM FcR expression, enabling AMs to release IL-18/IL-12 during lung infection. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Vardarova, S. Scharf, F. Lang, B. Schmeck, B. Opitz, J. Eitel, A. C. Hocke, H. Slevogt, A. Flieger, S. Hippenstiel, et al. PKC{alpha} and PKC{epsilon} differentially regulate Legionella pneumophila-induced GM-CSF Eur. Respir. J., November 1, 2009; 34(5): 1171 - 1179. [Abstract] [Full Text] [PDF] A. M. Guth, W. J. Janssen, C. M. 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	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020