Increased endothelial vesicular transport correlates with increased blood-tumor barrier permeability induced by bradykinin and leukotriene C4.
Bradykinin and leukotriene C4 (LTC4) have been shown to increase molecular transport across the blood-tumor barrier (BTB). The aim of this study was to quantitatively assess whether an increase in vesicular transport or opening of tight junctions was responsible for this increase in permeability. Wistar rats bearing RG2 or C6 gliomas were infused with bradykinin or LTC4 through the right carotid artery for 15 min and then perfused to achieve fixation. Prepared specimens were observed using transmission electron microscopy. Infusion of either bradykinin or LTC4 resulted in significantly increased vesicular density in capillary endothelial cells of the BTB but not in normal brain capillaries. The opening of tight junctions, assessed by determining a cleft index, was found to be greater in tumor capillaries compared to normal controls. However, neither bradykinin nor LTC4 produce variations in the cleft index. A significant accumulation of horseradish peroxidase was seen in the intercellular peri-capillary spaces and in endothelial transport vesicles after infusion of bradykinin, demonstrating that the formation of vesicles was associated with macromolecular transcytosis. These findings suggest that pinocytotic vesicular transport is the primary means by which luminal to abluminal transport occurs in response to vasomodulation with bradykinin or LTC4.
Hashizume
Kazuhiro
K
Maxine Dunitz Neurosurgical Institute, Cedars Sinai Medical Center, Los Angeles, California, USA.
Black
Keith L
KL
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000098:blood supply*; D002196:Capillaries / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005910:Glioma / Q000098:blood supply*; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D017997:Leukotriene C4 / Q000494:pharmacology*; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000187:drug effects / Q000648:ultrastructure
D017997:Leukotriene C4; D006735:Horseradish Peroxidase; D001920:Bradykinin