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The effect of glucocorticoids on the expression of L-selectin on polymorphonuclear leukocyte
M Nakagawa1, G P Bondy, D Waisman
1Pulmonary Research Laboratory, University of British Columbia, St Paul's Hospital, Vancouver, British Columbia, Canada.
Abstract:
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.
Insights
Glucocorticoids reduce L-selectin expression on circulating polymorphonuclear leukocytes (PMN) by suppressing synthesis in the bone marrow. This impacts PMN recruitment to inflammatory sites.
Area of Science:
- Immunology
- Hematology
- Pharmacology
Background:
- Inflammatory stimuli increase L-selectin on circulating polymorphonuclear leukocytes (PMN).
- Glucocorticoids induce granulocytosis and decrease L-selectin expression on PMN.
- The mechanism behind glucocorticoid-induced L-selectin reduction requires clarification.
Purpose of the Study:
- To investigate if glucocorticoid treatment suppresses L-selectin synthesis in bone marrow.
- To determine the effect of dexamethasone on L-selectin expression in PMN maturation.
Main Methods:
- New Zealand white rabbits received intravenous dexamethasone.
- L-selectin expression on circulating and bone marrow PMN was measured.
- Bone marrow PMN were pulse-labeled with 5'-bromo-2'-deoxyuridine (BrdU) to track newly released cells.
Main Results:
- Dexamethasone decreased L-selectin expression on circulating PMN 12-24 hours post-treatment.
- L-selectin expression on BrdU-labeled PMN released from bone marrow was significantly reduced.
- Dexamethasone decreased L-selectin on segmented PMN within the bone marrow, but not on circulating PMN.
Conclusions:
- Glucocorticoids decrease circulating PMN L-selectin by downregulating expression in the bone marrow maturation pool.
- This effect is a key mechanism by which glucocorticoids influence PMN recruitment to inflammation.
- The findings provide insight into the immunomodulatory effects of glucocorticoids.
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