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This Article Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Abdala-Valencia, H. Articles by Cook-Mills, J. PubMed Articles by Abdala-Valencia, H. Articles by Cook-Mills, J.

Non-hematopoietic NADPH Oxidase Regulation of Lung Eosinophilia and Airway Hyperresponsiveness in Experimentally-Induced Asthma

¹ Allergy/Immunology, Northwestern Univ. Feinberg School of Med., 240 E. Huron, Chicago, IL, 60611, ² Pathology, Univ. of Cincinnati, PO Box 670529, Cincinnati, OH, 45267-0529, ³ University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267-0558, ⁴ Univ. of Kentucky, 800 Rose Street, Lexington, KY, 40536-0298, ⁵ Cincinnati Children’s Hosp. Res. Fndn, 3333 Burnet Avenue, Cincinnati, OH, 45229

Abstract

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 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, IFNã, 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.

(supported by NIH HL069428, J.M.C-M.)

This Article Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Abdala-Valencia, H. Articles by Cook-Mills, J. PubMed Articles by Abdala-Valencia, H. Articles by Cook-Mills, J.