Granulocyte-macrophage colony-stimulating factor crosses the blood--brain and blood--spinal cord barriers.
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.
McLay
R N
RN
Neuroscience Training Program, Tulane University, New Orleans, Louisiana, USA.
Kimura
M
M
Banks
W A
WA
Kastin
A J
AJ
D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002490:Central Nervous System / Q000098:blood supply* / Q000378:metabolism*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008833:Microcirculation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
D000418:Albumins; D007457:Iodine Radioisotopes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor