HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Noulin, N. Articles by Couillin, I. Search for Related Content PubMed PubMed Citation Articles by Noulin, N. Articles by Couillin, I.

Both Hemopoietic and Resident Cells Are Required for MyD88-Dependent Pulmonary Inflammatory Response to Inhaled Endotoxin¹

Nicolas Noulin^*,, Valérie F. J. Quesniaux^*, Silvia Schnyder-Candrian^*, Bruno Schnyder^*,, Isabelle Maillet^*,, Thomas Robert^*, B. Boris Vargaftig, Bernhard Ryffel^* and Isabelle Couillin^2,*,

^* Centre National de la Recherche Scientifique Transgenose Institute, Orleans, France; Key-Obs S. A., Orleans, France, Department of Pharmacology, Instituto de Ciências Biomédicas, University of São Paulo, São Paulo, Brazil; and Biomedical Research Foundation, Matzingen, Switzerland

Inhaled endotoxin induces an inflammatory response that contributes to the development and severity of asthma and other forms of airway disease. Here, we show that inhaled endotoxin-induced acute bronchoconstriction, TNF, IL-12p40, and KC production, protein leak, and neutrophil recruitment in the lung are abrogated in mice deficient for the adaptor molecule MyD88. Bronchoconstriction, inflammation, and protein leak are normal in Toll/IL-1R domain-containing adaptor inducing IFN--deficient mice. MyD88 is involved in TLR, but also in IL-1R-associated kinase 1-mediated IL-1R and -18R signaling. We exclude a role for IL-1 and IL-18 pathways in this response, as IL-1R1 and caspase-1 (ICE)-deficient mice develop lung inflammation while TLR4-deficient mice are unresponsive to inhaled LPS. Significantly, using bone marrow chimera, we demonstrate that both hemopoietic and resident cells are necessary for a full MyD88-dependent response to inhaled endotoxin; bronchoconstriction depends on resident cells while cytokine secretion is mediated by hemopoietic cells.