The effect of glucocorticoids on the expression of L-selectin on polymorphonuclear leukocyte.
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.
Nakagawa
M
M
Pulmonary Research Laboratory, University of British Columbia, St Paul's Hospital, Vancouver, British Columbia, Canada.
Bondy
G P
GP
Waisman
D
D
Minshall
D
D
Hogg
J C
JC
van Eeden
S F
SF
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007700:Kinetics; D019041:L-Selectin / Q000097:blood / Q000235:genetics*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D013997:Time Factors
D005938:Glucocorticoids; D019041:L-Selectin; D003907:Dexamethasone