Glucocorticoid-induced granulocytosis: contribution of marrow release and demargination of intravascular granulocytes.
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.


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 approximately 10%, mobilization from the marginated pool approximately 61%, and a lengthened half-life in the circulation approximately 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.
Nakagawa
M
M
Pulmonary Research Laboratory, University of British Columbia, St Paul's Hospital, Vancouver, BC, Canada.
Terashima
T
T
D'yachkova
Y
Y
Bondy
G P
GP
Hogg
J C
JC
van Eeden
S F
SF
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006098:Granulocytes / Q000187:drug effects* / Q000473:pathology; D007275:Injections, Intravenous; D007958:Leukocyte Count / Q000187:drug effects; D007964:Leukocytosis / Q000097:blood / Q000139:chemically induced / Q000473:pathology*; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D011817:Rabbits; D013997:Time Factors
D003907:Dexamethasone; D001973:Bromodeoxyuridine