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RK Shadduck, A Waheed and EJ Wing
Department of Medicine, Montefiore Hospital, Pittsburgh, PA 15213.
Several previous studies suggested that murine macrophage colony-
stimulating factor (CSF-1) might have impaired access to hematopoietic
cells in the marrow. The apparent lack of hematopoietic responses to
exogenous CSF and the finding of available or unoccupied CSF receptors
despite saturating CSF levels in the serum led to studies of a potential
blood-bone marrow barrier for this factor. Groups of mice were injected
with pure unlabeled CSF-1 by either intravenous (IV) or intraperitoneal
(IP) routes. Marrow and spleen cells were obtained at intervals after
injection, held at 0 degree C, and assessed for changes in binding of
125I-CSF. Saturation of all available CSF receptors is achieved in vitro
with 100 to 150 U CSF/mL. Despite achieving serum levels of 5,000 to 7,000
U/mL after IV injection of 25,000 units of CSF, less than 50% of the marrow
receptors and less than 85% of the splenic receptors were saturated or
downregulated. The decline in receptor availability was transient, with
return of receptor sites in two to four hours. Increasing the IV dose to
125,000 units increased serum CSF values to approximately 20,000 U/mL and
led to a virtual disappearance of available receptors for two to three
hours. When administered IP, only approximately 40% of marrow and 80% of
splenic receptors were affected for two hours. It was necessary to increase
the dose of CSF to 250,000 units IP to saturate or downregulate receptors
for three to four hours after injection. These observations indicate a
marked blood-bone marrow barrier and lesser blood-spleen barrier for the
transfer of serum CSF to responsive hematopoietic cells in vivo.
This article has been cited by other articles:
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| Copyright © 1989 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
