Brain, Vol 120, Issue 11 2083-2091, Copyright © 1997 by Oxford University Press
RN McLay, M Kimura, WA Banks and AJ Kastin
Granulocyte-macrophage colony-stimulating factor (GM-CSF), a glycoprotein
with hormonal properties, is produced by several cell types, most of which
exist outside the CNS. GM-CSF, however, affects the CNS. If capable of
crossing from blood to CNS, GM-CSF might be an important signalling
molecule between the CNS and periphery. We used an established in vivo
method in mice and rats to study passage of radioactively labelled GM-CSF
from blood to CNS. We found that GM-CSF crossed the blood-brain barrier and
blood-spinal cord barrier significantly faster than the control substance,
albumin. Labelled GM- CSF was recovered in intact form by high performance
liquid chromatography from brain after peripheral injection, and passage
was not significantly reduced by simultaneous injection of unlabelled L-
tryptophan. Both findings indicate that the observed passage of
radioactivity was intact protein. Capillary depletion experiments showed
that most of the GM-CSF was deposited in brain parenchyma rather than
cerebral capillary endothelium. Co-injection of unlabelled GM-CSF
significantly reduced the passage rate of labelled cytokine across the
blood-brain and blood-spinal cord barriers, demonstrating that passage was
mediated by a saturable system. In summary, a saturable mechanism
transports GM-CSF intact from blood to CNS.
ARTICLES
Granulocyte-macrophage colony-stimulating factor crosses the blood-- brain and blood--spinal cord barriers
Neuroscience Training Program, Tulane University, New Orleans, Louisiana, USA.
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