Effect of inhaled endotoxin on airway and circulating inflammatory cell phagocytosis and CD11b expression in atopic asthmatic subjects.
BACKGROUND
In a cohort of 8 normal and 10 allergic asthmatic volunteers, we previously reported that inhalation of 5 microg 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.
Alexis
Neil E
NE
Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, 27599, USA.
Eldridge
Marlowe W
MW
Peden
David B
DB
D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D001773:Blood Cells / Q000502:physiology*; D039481:CD11b Antigen / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000150:complications*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008566:Membranes / Q000378:metabolism; D010586:Phagocytes / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D012129:Respiratory Function Tests; D013183:Sputum / Q000166:cytology / Q000187:drug effects
D039481:CD11b Antigen; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides