Volume 112, Issue 2 , Pages 353-361, August 2003
Effect of inhaled endotoxin on airway and circulating inflammatory cell phagocytosis and CD11b expression in atopic asthmatic subjects☆☆☆★
Abstract
Background: In a cohort of 8 normal and 10 allergic asthmatic volunteers, we previously reported that inhalation of 5 μg of endotoxin (LPS) induced airway inflammation that correlated with CD14 expression that was, in turn, correlated with eosinophil numbers in the airway. Macrophage and neutrophil functions have been reported to be modified by endotoxin in vitro and in vivo, and response to endotoxin is mediated largely by airway phagocytes and related to allergic inflammation. Objective: We sought to examine functional and cell-surface phenotype changes in phagocytes recovered from atopic asthmatic subjects after endotoxin challenge. Methods: Sputum and peripheral blood from 10 allergic asthmatic subjects was recovered after saline and LPS challenge. Assessment of phagocytosis and cell-surface phenotype (CD11b, CD14, and CD64) was performed on phagocytes obtained from sputum (n = 7) and blood samples (n = 10). Results: Phagocytosis of blood and sputum phagocytes was blunted after LPS challenge in a fashion that correlated with the increase in airway neutrophils after LPS challenge. Cell-surface expression of CD14 (membrane-bound CD14) was increased in sputum cells, whereas CD11b was decreased in sputum and circulating phagocytes. Baseline expression of CD11b in blood correlated with the magnitude of the neutrophil response after LPS inhalation, as well as (inversely) with baseline airway eosinophil levels. Conclusions: Inhalation of endotoxin at levels adequate to induce a neutrophil influx to the airways (but not systemic symptoms) results in decreased phagocytosis in both airway and circulating cells and modifies CD11b expression in a way that implicates its involvement in phagocyte responsiveness to inhaled LPS. (J Allergy Clin Immunol 2003;112:353-61.)
Keywords: Endotoxin, phagocytosis, CD11b, neutrophil response
Abbreviations: ARDS: , Acute respiratory distress syndrome, CR3: , Complement receptor 3, MFI: , Mean fluorescence intensity
☆ Supported by US Environmental Protection Agency grant CR-824915, National Institutes of Health grant 1RO1HL62624-01, and National Institutes of Environmental Health Science grant NO1-ES-35356.
☆☆ Although the research described in this article has been funded wholly or in part by the United States Environmental Protection Agency through cooperative agreement CR829522 with the Center for Environmental Medicine, Asthma and Lung Biology at the University of North Carolina at Chapel Hill, it has not been subjected to the Agency's required peer and policy review and therefore does not necessarily reflect the views of the Agency, and no official endorsement should be inferred. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.
★ Reprint requests: David B. Peden, MD, MS, Center for Environmental Medicine, Asthma and Lung Biology 104 Mason Farm Rd, University of North Carolina School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7310.
PII: S0091-6749(03)01622-1
doi:10.1067/mai.2003.1651
© 2003 Mosby, Inc. All rights reserved.
Volume 112, Issue 2 , Pages 353-361, August 2003
