Lhk. Lim et al., Glucocorticoid receptor activation reduces CD11b and CD49d levels on murine eosinophils - Characterization and functional relevance, AM J RESP C, 22(6), 2000, pp. 693-701
Citations number
45
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
In vitro incubation of mouse blood eosinophils with dexamethasone (DEX) res
ulted in concentration- and time-dependent reduction in CD11b and CD49d cel
l-surface expression as detected by flow cytometry. This inhibitory effect
ranged between 20 and 40% for both integrins, and it was not related to alt
eration of cell survival. DEX was maximally effective at 1 mu M, and it was
prevented by coaddition of the glucocorticoid receptor antagonist RU486 (m
ifepristone; 10 mu M). Budesonide, hydrocortisone, and prednisolone, but no
t the sex steroids testosterone and progesterone, reduced CD11b and CD49d c
ell-surface expression to a similar extent. Subchronic treatment of mice wi
th 1 mg/kg DEX again reduced both CD11b and CD49d expression on circulating
eosinophils, without alterations in CD11b messenger RNA expression as asse
ssed by polymerase chain reaction analysis. In contrast, membrane but not i
ntracellular protein expression of either CD11b or CD49d was inhibited by e
osinophil incubation with DEX in vitro; thus, an interference with exportat
ion of these adhesion molecules to the cell surface is proposed as the mech
anism of action of the glucocorticoid. Finally, steroid effects on integrin
expression were linked to a reduced eosinophil function as indicated by a
lower degree of cell chemotaxis after incubation with DEX, an effect which
was again prevented by 10 mu M RU486, These observations may explain part o
f the therapeutic efficacy displayed by glucocorticoid hormones in the clin
ical control of tissue eosinophilia in allergic disease conditions.