(Circulation. 1998;98:2307-2313.)
© 1998 American Heart Association, Inc.
Basic Science Reports |
Glucocorticoid-Induced Granulocytosis
Contribution of Marrow Release and Demargination of Intravascular Granulocytes
From the Pulmonary Research Laboratory, University of British Columbia, St Paul's Hospital, Vancouver, BC, Canada.
Correspondence to Dr S.F. van Eeden, University of British Columbia, Pulmonary Research Laboratory, St Paul's Hospital, 1081 Burrard St, Vancouver, BC, Canada, V6Z1Y6. E-mail svaneeden{at}prl.pulmonary.ubc.ca
Background—Glucocorticoid-induced granulocytosis has been attributed to enhanced release of polymorphonuclear leukocytes (PMNs) from bone marrow, delayed apoptosis, and reduced egress of PMNs into tissues. This study was designed to determine the relative contributions of PMNs released from the bone marrow and those entering the circulation from the marginated pool to the granulocytosis produced by a single dose of dexamethasone (2.0 mg/kg) in rabbits.
Methods and Results—PMN transit through the mitotic and
postmitotic pools of the bone marrow and rate of release of PMNs into
the circulation were measured by use of the thymidine analogue
5'-bromo-2'-deoxyuridine (BrdU) to pulse-label PMNs in the bone marrow.
The shift of PMNs from the marginated to the circulating pool was
measured with BrdU-labeled PMNs transferred from donor rabbits to
recipients before dexamethasone was delivered. The data
show that dexamethasone increased bone marrow release of
PMNs and shortened their transit time through the postmitotic pool
(P<0.001) but not the mitotic pool of the bone marrow
(P>0.05). Dexamethasone slowed the
clearance of BrdU-labeled PMNs from the circulation
(P<0.05) and lengthened their disappearance (half-life)
from the circulation compared with control (half-life, 4.95 versus 9.45
hours). At 6 hours after dexamethasone, bone marrow release
contributed 
10%, mobilization from the marginated pool 61%, and
a lengthened half-life in the circulation 29% to the
glucocorticoid-induced granulocytosis.
Conclusions—We conclude that a single dose of dexamethasone causes a granulocytosis primarily by a shift of PMNs from the marginated to the circulating pool, with a minor contribution from marrow release.
Key Words: leukocytes • microcirculation • hormones • immunohistochemistry
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