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Blood, Vol. 93 No. 8 (April 15), 1999: pp. 2730-2737

The Effect of Glucocorticoids on the Expression of L-Selectin on Polymorphonuclear Leukocyte

Motohito Nakagawa, Gregory P. Bondy, Dan Waisman, Diane Minshall, James C. Hogg, and Stephan F. van Eeden

From the Pulmonary Research Laboratory, University of British Columbia, St Paul's Hospital, Vancouver, British Columbia, Canada; and the Department of Neonatology, Carmel Medical Center, Faculty of Medicine, Technion, Harif, Israel.

When active bone marrow release is induced by inflammatory stimuli, it is associated with an increase in L-selectin expression on circulating polymorphonuclear leukocyte (PMN). This contrasts sharply with glucocorticoid-induced granulocytosis that is associated with decreased L-selectin expression on PMN. The present study was designed to determine if the reduced L-selectin expression observed after glucocorticoid treatment is the result of suppression of L-selectin synthesis in the bone marrow. New Zealand white rabbits treated with dexamethasone (2.0 mg/kg, a single dose intravenously) were shown to have decreased L-selectin expression on circulating PMN 12 to 24 hours after treatment (P < .01) with a return to baseline levels by 48 hours. When dexamethasone was administered 48 hours after the bone marrow PMN were pulse labeled with the thymidine analogue, 5'-bromo-2'-deoxyuridine (BrdU), L-selectin expression on BrdU-labeled PMN released from the bone marrow was decreased (P < .01). Dexamethasone decreased L-selectin expression on segmented PMN in the bone marrow (P < .05) but not on PMN already in the circulation. We conclude that glucocorticoids decrease L-selectin expression on circulating PMN by downregulating L-selectin expression in the maturation pool of bone marrow and speculate that this is an important glucocorticoid effect that influences the recruitment of PMN into inflammatory sites.


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