The microcirculation functions to provide rapid exchange of nutrients and waste products between blood and tissues. Large molecules, such as plasma proteins, exit most capillaries at low rates and by two routes: (1) vesicular transport via the shuttling of 50- to 70-nm cytoplasmic vesicles present in endothelial cells (or by interconnected vesicles that form transendothelial cell channels), and (2) interendothelial cell gaps.
We identified a new endothelial cell organelle, which we termed the vesiculo-vacuolar organelle (VVO) (Figure 1) . This organelle provides the major route of extravasation of macromolecules at sites of augmented vascular permeability induced by vascular permeability factor/ vascular endothelial growth factor (VPF/VEGF), a tumor-derived cytokine, in venules associated with experimental tumors [1, 2]. We also reported extensive VVOs in venular endothelium in an animal model of allergic inflammatory eye disease, characterized by histamine secretion from augmented mast cell expression. Further studies used multiple ultrastructural methods to determine (1) the substructure and contents of VVOs, (2) the formation of VVOs, (3) the mechanism of upregulated function of VVOs, and (4) whether tumor cytokines and mediators of inflammation with permeabilizing properties could recapitulate in normal vessels the upregulated VVO function of tumor vessels .
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This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.