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) All Versions of this Article: 292/5/L1111    most recent 00208.2006v1 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 (3) Citing Articles via Google Scholar Google Scholar Articles by Abdala-Valencia, H. Articles by Cook-Mills, J. M. Search for Related Content PubMed PubMed Citation Articles by Abdala-Valencia, H. Articles by Cook-Mills, J. M.

Nonhematopoietic NADPH oxidase regulation of lung eosinophilia and airway hyperresponsiveness in experimentally induced asthma

¹Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois; ²Department of Pathology and Laboratory Medicine, University of Cincinnati; ³Division of Immunobiology and ⁴Division of Experimental Hematology, Cincinnati Children's Hospital Research Foundation; ⁵Department of Surgery, College of Medicine, University of Cincinnati and Shriners Hospitals for Children, Cincinnati, Ohio; and ⁶Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky Chandler Medical Center, Lexington, Kentucky

Submitted 8 June 2006 ; accepted in final form 31 January 2007

Pulmonary eosinophilia is one of the most consistent hallmarks of asthma. Infiltration of eosinophils into the lung in experimental asthma is dependent on the adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells. Ligation of VCAM-1 activates endothelial cell NADPH oxidase, which is required for VCAM-1-dependent leukocyte migration in vitro. To examine whether endothelial-derived NADPH oxidase modulates eosinophil recruitment in vivo, mice deficient in NADPH oxidase (CYBB mice) were irradiated and received wild-type hematopoietic cells to generate chimeric CYBB mice. In response to ovalbumin (OVA) challenge, the chimeric CYBB mice had increased numbers of eosinophils bound to the endothelium as well as reduced eosinophilia in the lung tissue and bronchoalveolar lavage. This occurred independent of changes in VCAM-1 expression, cytokine/chemokine levels (IL-5, IL-10, IL-13, IFN, or eotaxin), or numbers of T cells, neutrophils, or mononuclear cells in the lavage fluids or lung tissue of OVA-challenged mice. Importantly, the OVA-challenged chimeric CYBB mice had reduced airway hyperresponsiveness (AHR). The AHR in OVA-challenged chimeric CYBB mice was restored by bypassing the endothelium with intratracheal administration of eosinophils. These data suggest that VCAM-1 induction of NADPH oxidase in the endothelium is necessary for the eosinophil recruitment during allergic inflammation. Moreover, these studies provide a basis for targeting VCAM-1-dependent signaling pathways in asthma therapies.

endothelium; gp91 phox; eosinophils; VCAM-1

This article has been cited by other articles:

				H. H. Norris, M. E. Peterson, C. C. Stebbins, B. W. McConchie, V. G. Bundoc, S. Trivedi, M. G. Hodges, R. M. Anthony, J. F. Urban Jr, E. O. Long, et al. Inhibitory receptor gp49B regulates eosinophil infiltration during allergic inflammation J. Leukoc. Biol., December 1, 2007; 82(6): 1531 - 1541. [Abstract] [Full Text] [PDF]