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Polymorphonuclear leukocytes released from the bone marrow by granulocyte colony-stimulating factor: intravascular
1Pulmonary Research Laboratory, University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia, V6Z1Y6, Canada.
Introduction:
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.
Materials And 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).
Conclusion:
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.
Insights
Granulocyte-colony stimulating factor (G-CSF) reduces polymorphonuclear leukocyte (PMN) sequestration in the lungs and prolongs their survival in circulation. This G-CSF effect enhances PMN availability and function.
Area of Science:
- Hematology
- Immunology
- Pharmacology
Background:
- Granulocyte-colony stimulating factor (G-CSF) is known to stimulate bone marrow activity.
- G-CSF treatment leads to the release of polymorphonuclear leukocytes (PMN) into the bloodstream.
- Understanding the behavior of G-CSF-released PMN is crucial for their therapeutic applications.
Purpose of the Study:
- To quantify the intravascular margination, demargination, and survival of PMN following G-CSF administration.
- To investigate the impact of G-CSF on PMN trafficking and lifespan in the circulation.
Main Methods:
- Rabbits were administered a single dose of G-CSF (12.5 microg/kg).
- Bone marrow PMN were labeled with 5'-bromo-2'-deoxyuridine (BrdU) to trace their circulation.
- Lung microvessel sequestration and PMN clearance rates were measured in G-CSF treated and control groups.
Main Results:
- G-CSF induced granulocytosis, peaking at 12 hours, with shortened PMN transit time in bone marrow.
- Reduced sequestration of BrdU-labeled PMN in lung microvessels was observed in G-CSF treated animals.
- G-CSF treatment inhibited apoptosis in circulating PMN, leading to delayed clearance and prolonged intravascular lifespan.
Conclusions:
- PMN released by G-CSF exhibit reduced sequestration in lung microvasculature.
- G-CSF treatment extends the intravascular lifespan of circulating PMN.
- These findings suggest G-CSF enhances PMN availability and function through improved trafficking and survival.