The induction of ICAM-1 in human cerebromicrovascular endothelial cells (HCEC) by ischemia-like conditions promotes enhanced neutrophil/HCEC adhesion.
Ischemic brain injury is exacerbated by leukocyte infiltration and formation of vasogenic edema. In this study we demonstrate that intercellular adhesion molecule-1 (ICAM-1) is dramatically (3 to 15-fold) up-regulated in human cerebromicrovascular endothelial cells (HCEC) by a 16 h exposure to the cytokine, IL-1 beta (50-200 u/ml), the phorbol ester, TPA (1-100 nM), or by simulated in vitro ischemia/reperfusion. These treatments also significantly increased the adhesion of allogeneic neutrophils to HCEC monolayers. Both IL-1 beta- and TPA-induced expression of ICAM-1 and increased neutrophil adhesion to HCEC were inhibited by the transcriptional inhibitor, actinomycin D (AcD; 1-10 micrograms/ml), and by an anti-ICAM-1 antibody (ICAM-1 Ab). By contrast, ischemia-induced neutrophil adhesion was only slightly affected by AcD and ICAM-1 Ab alone, but it was abolished by the combination of anti-ICAM-1 and anti-CD18 antibodies. The increase in surface expression of ICAM-1 and neutrophil adhesion by IL-1 beta, TPA and ischemia were significantly reduced by the cyclo-oxygenase (COX) inhibitors, indomethacin (100-300 microM) and dexamethasone (10-50 microM). These results indicate that ICAM-1 expression in HCEC can lead to enhanced neutrophil adhesion and that COX activation in HCEC likely plays a role in the processes by which leukocyte adhesion and recruitment take place in the brain during inflammation and ischemia in vivo.
Stanimirovic
D
D
Cellular Neurobiology Group, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ont., Canada. danica.stanimirovic@biologym54.lan.nrc.ca
Shapiro
A
A
Wong
J
J
Hutchison
J
J
Durkin
J
J
D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply*; D002545:Brain Ischemia / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007375:Interleukin-1; D018799:Intercellular Adhesion Molecule-1; D011451:Prostaglandin-Endoperoxide Synthases; D013755:Tetradecanoylphorbol Acetate