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Published online before print February 3, 2004

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(Journal of Leukocyte Biology. 2004;75:815-827.)
© 2004 by Society for Leukocyte Biology

Mechanisms of glucocorticoid-induced down-regulation of neutrophil L-selectin in cattle: evidence for effects at the gene-expression level and primarily on blood neutrophils

Patty S. D. Weber^*, Trine Toelboell^*, Ling-Chu Chang^*, Janelle Durrett Tirrell^*, Peter M. Saama, George W. Smith^, and Jeanne L. Burton^*,,1

^* Immunogenetics Laboratory,
Center for Animal Functional Genomics, Department of Animal Science, and
Molecular Reproduction Laboratory, Departments of Animal Science and of Physiology, Michigan State University, East Lansing

¹Correspondence: Department of Animal Science, 1205E Anthony Hall, Michigan State University, East Lansing, MI 48824. E-mail: burtonj{at}msu.edu

One anti-inflammatory action of glucocorticoids is down-regulation of surface L-selectin on circulating neutrophils. However, it is unclear if this is a result of release of affected bone marrow neutrophils or if the steroid has direct effects on L-selectin expression in existing blood neutrophils. We recently demonstrated that circulating neutrophils from cattle with high blood concentrations of endogenous glucocorticoid had reduced L-selectin mRNA, suggesting that the steroid interrupted L-selectin gene expression. In the current study, dexamethasone (DEX) was administered to cattle in vivo, and blood and bone marrow neutrophils were studied simultaneously within the animal to determine which pool of cells responds to glucocorticoids with inhibited L-selectin expression. Purified blood neutrophils were also treated with DEX ± RU486 in vitro, and glucocorticoid effects on L-selectin expression were determined. Our results indicate that glucocorticoid-induced suppression of L-selectin, which accompanies neutrophilia, is likely mediated by direct effects of glucocorticoid receptor activation on intracellular reservoirs of L-selectin mRNA and protein in cattle, predominantly in blood neutrophils.

Key Words: CD62L • bone marrow • bovine

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