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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.
Summary
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.