Adhesion Molecules in Cerebral Ischemia and Atherosclerosis

Cengiz, Nureddin; Erdoğan, Ender; Özbek, Hanefí; Tuncer, Mustafa

doi:10.29333/ejgm/82678

Cited by 1 publication

(1 citation statement)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The phenotype of MV released from activated cells contains overlapping as well as distinct protein compositions, depending upon the cell of origin as well as the stimulus which initiated their generation [14, 15]. For example, platelet endothelial cell adhesion molecule-1 (PECAM-1), integrin αvβ3, intercellular adhesion molecule-1 (ICAM-1), E-selectin, and melanoma cell adhesion molecule/cell surface glycoprotein MUC18 (MCAM) are upregulated in human cerebrovascular endothelial cells under inflammatory conditions and mediate a multi-step process resulting in transmigration of immune cells into the brain [16–20]. E-selectin, which is expressed specifically on activated endothelial cells, is rapidly induced and binds with low affinity to ligands on various cell types for their recruitment to sites of inflammation.…”

Section: Introductionmentioning

confidence: 99%

Sex differences in the expression of cell adhesion molecules on microvesicles derived from cultured human brain microvascular endothelial cells treated with inflammatory and thrombotic stimuli

2019

View full text Add to dashboard Cite

Background There are sex differences in risk for stroke and small vessel ischemic disease in the brain. Microvesicles (MV) derived from activated cells vary by cell of origin and the stimulus initiating their release. MV released from cells activated by inflammatory and thrombotic factors have the potential to disrupt endothelial cells of the brain microvasculature. Therefore, experiments were designed to identify sex differences in the phenotype of MV released from cultured human brain microvascular endothelial cells (HBMEC) in response to inflammatory and thrombotic stimuli. Methods Cultured HBMEC derived from 20- to 30-year-old male and female donors were treated for 20 h with medium supplemented with tumor necrosis factor alpha (TNFα; 20 ng/ml), thrombin (THR; 2 U/ml), or vehicle (i.e., control). MV were isolated from the conditioned media by high-speed centrifugation and quantified by digital flow cytometry by labeling with fluorophore-conjugated primary antibodies against PECAM-1, integrin αvβ3, ICAM-1, E-selectin, or MCAM. In addition, temporal uptake of labeled MV into control HBMEC was examined by confocal microscopy. Results Under control conditions, male HBMEC released fewer MV expressing each antigen, except for PECAM-1, than female cells ( P < 0.05). Neither TNFα nor THR reduced cell viability. However, TNFα induced apoptosis in female and male cells, whereas THR increased apoptosis marginally only in male cells. TNFα increased expression of all antigens tested on MV in male cells, but only increased expression of integrin αvβ3, ICAM-1, and E-selectin on MV from female cells. THR increased expression of PECAM-1, ICAM-1, and MCAM-1 on MV from male but not female cells. MV were internalized and localized to lysosomes within 90 min after their application to HBMEC. Conclusions There are sex differences in expression of cell adhesion molecules on MV released from HBMEC under control conditions and upon activation by TNFα or THR. MV taken up by unstimulated HBMEC may impact the integrity of the brain microvasculature and account, in part, for sex differences in vascular pathologies in the brain.

show abstract