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Endotoxin: a twofold effect on bone marrow ultrastructure
T Hirahata1, D Bjorkman, J K Chamberlain
1East Carolina University School of Medicine, Greenville, NC 27858-4354.
Abstract:
Ultrastructural studies of mouse bone marrow reveal that reduction of the marrow-blood barrier precedes the two waves of leukocytosis which follow endotoxin administration. These ultrastructural changes include a decrease in adventitial cover of the marrow sinus wall, an increase in sinus circumference, and a decrease in endothelial cell overlap. The marrow-blood barrier changes which precede the first wave of leukocytosis are transient and are associated with depletion of marrow granulocytes. The changes that precede the second wave of leukocytosis 5 to 6 days later are more sustained and are associated with marked granulocyte hyperplasia. We suggest that endotoxin has two effects on marrow ultrastructure: (1) an early, direct effect on the sinus wall and (2) a later, indirect effect associated with granulocyte proliferation. The late effect may be mediated through endotoxin induced release of colony stimulating factor. Both effects diminish the normal marrow-blood barrier and appear to facilitate cell release from the marrow.
Insights
Endotoxin administration temporarily weakens the mouse bone marrow barrier, facilitating white blood cell release. This occurs in two waves, linked to granulocyte changes and hyperplasia.
Area of Science:
- Hematology
- Cell Biology
- Immunology
Background:
- Endotoxin administration triggers significant physiological responses, including changes in leukocyte counts.
- The bone marrow serves as a critical site for leukocyte production and release.
- Understanding the regulation of the marrow-blood barrier is key to comprehending leukocyte mobilization.
Purpose of the Study:
- To investigate the ultrastructural changes in the mouse bone marrow barrier following endotoxin administration.
- To correlate these ultrastructural changes with the observed waves of leukocytosis.
- To elucidate the mechanisms underlying endotoxin-induced alterations in marrow-blood barrier integrity.
Main Methods:
- Ultrastructural analysis of mouse bone marrow using electron microscopy.
- Observation of changes in the marrow sinus wall, including adventitial cover, sinus circumference, and endothelial cell overlap.
- Correlation of ultrastructural findings with temporal patterns of leukocytosis.
Main Results:
- Reduction in the marrow-blood barrier precedes two distinct waves of leukocytosis after endotoxin exposure.
- Early barrier changes are transient, associated with granulocyte depletion; later changes are sustained, linked to granulocyte hyperplasia.
- Observed ultrastructural alterations include decreased adventitial cover, increased sinus circumference, and reduced endothelial cell overlap.
Conclusions:
- Endotoxin exerts both early, direct effects on the sinus wall and later, indirect effects possibly mediated by colony-stimulating factor.
- These dual effects compromise the marrow-blood barrier, enhancing leukocyte release.
- The findings provide insights into the dynamic regulation of leukocyte egress from the bone marrow.