Radiation-induced up-regulation of adhesion molecules in brain microvasculature and their modulation by dexamethasone.
Little is known about the time course and magnitude of the up-regulation of endothelial cell adhesion molecules (ECAMs) in irradiated brain vasculature and the mechanisms by which dexamethasone modulates this up-regulation. We used antibody-conjugated microspheres and a rat closed cranial window model to determine the time course of functional up-regulation of radiation (20 Gy)-induced ICAM1, E-selectin and P-selectin in the pial vasculature of the rat brain and to determine the relationship between suppression of inflammation by dexamethasone and the expression of these ECAMs. The results indicate that ICAM1, E-selectin and P-selectin were up-regulated to a functional level in the microvasculature with distinct time-course patterns. The number of adherent anti-E-selectin and anti-P-selectin microspheres was 5- 12 times greater than that of IgG microspheres 3-6 h postirradiation, and their expression returned to normal at 48 h. The number of adherent anti-ICAM1 microspheres was five and nine times greater than that of IgG at 24 and 48 h, respectively, and returned to baseline by 7 days. Dexamethasone significantly reduced the number of adhering leukocytes and the number of adhering anti-ICAM1, anti-E-selectin and anti-P-selectin microspheres to background levels. Our findings partially identify a key sequence in radiation-induced inflammatory response and provide a potential means to limit radiation-induced inflammatory responses and their potential side effects in the brain.
Yuan
Hong
H
Department of Biomedical Engineering, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Goetz
Douglas J
DJ
Gaber
M Waleed
MW
Issekutz
Andrew C
AC
Merchant
Thomas E
TE
Kiani
Mohammad F
MF
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000528:radiation effects*; D002448:Cell Adhesion / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D019040:E-Selectin / Q000235:genetics*; D005786:Gene Expression Regulation / Q000528:radiation effects*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D007962:Leukocytes / Q000502:physiology / Q000528:radiation effects; D008297:Male; D008833:Microcirculation / Q000378:metabolism / Q000528:radiation effects; D008863:Microspheres; D019007:P-Selectin / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D019040:E-Selectin; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone