Polymorphonuclear leukocytes released from the bone marrow by granulocyte colony-stimulating factor: intravascular behavior.
BACKGROUND
Granulocyte-colony stimulating factor (G-CSF) treatment stimulates the bone marrow and releases polymorphonuclear leukocytes (PMN) into the circulation. This study was designed to measure the intravascular margination, demargination and survival of PMN released from the marrow by G-CSF.


METHODS
To trace PMN in the circulation, dividing PMN in the bone marrow of rabbits were labeled with 5'-bromo-2'-deoxyuridine (BrdU) and the effects of a single dose of G-CSF (12.5 microg/kg) on the behavior of these labeled cells in the circulation were measured.


RESULTS
The results show that G-CSF induced a granulocytosis that peaked 12 h after treatment. This granulocytosis was associated with stimulation of the bone marrow characterized by shortening of the transit time of PMN through the marrow (97.3+/-2.5 h n=4 control vs 78.9+/-3.6 h n=5 G-CSF) particularly in the post-mitotic pool (P<0.01). Morphometric studies of the lung show a reduced sequestration of BrdU-labeled PMN in lung microvessels in G-CSF-treated animals (P<0.05) and a approximately 14-fold (G-CSF-group) vs a approximately 65-fold (control-group) enrichment of BrdU-labeled PMN in lung tissue if compared to circulating blood. The effect of G-CSF on demargination of PMN was measured by transferring BrdU-labeled PMN from donor animals treated with G-CSF to recipients. G-CSF did not cause demargination of intravascular PMN but delayed the clearance of G-CSF-treated PMN in the circulation. This delayed clearance was associated with inhibition of apoptosis in circulating PMN when measured both by morphology (17.7+/-2.3 vs 7.5+/-1.4%, P<0.01) and flow cytometry (16.2+/-1.1 vs 5+/-1.9%, P<0.01) using a DNA end-labeling method (control vs G-CSF group).


CONCLUSIONS
We conclude that PMN released from the bone marrow by G-CSF sequestered less in the lung microvessels and have a prolonged intravascular life span.
Mukae
H
H
Pulmonary Research Laboratory, University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia, V6Z1Y6, Canada.
Zamfir
D
D
English
D
D
Hogg
J C
JC
van Eeden
S F
SF
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D001973:Bromodeoxyuridine; D002470:Cell Survival / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D007958:Leukocyte Count; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects; D011817:Rabbits
D016179:Granulocyte Colony-Stimulating Factor; D001973:Bromodeoxyuridine