REINTERPRETATION OF ENDOTHELIAL-CELL GAPS INDUCED BY VASOACTIVE MEDIATORS IN GUINEA-PIG, MOUSE AND RAT - MANY ARE TRANSCELLULAR PORES

1. In response to vascular permeabilizing agents, particulates circula ting in the blood extravasate from venules through endothelial cell op enings. These openings have been thought to be intercellular gaps thou gh recently this view has been challenged. 2. To define the precise lo cation of endothelial cell gaps, serial section electron microscopy an d three-dimensional reconstructions were performed in skin and cremast er muscle of guineapigs, mice and rats injected locally with agents th at enhance microvascular permeability: vascular permeability factor, h istamine or serotonin. Ferritin and colloidal carbon were injected int ravenously as soluble and particulate macromolecular tracers, respecti vely. 3. Both tracers extravasated from venules in response to all thr ee permeability enhancing agents. The soluble plasma protein ferritin extravasated primarily by way of vesiculo-vacuolar organelles (VVOs), interconnected clusters of vesicles and vacuoles that traverse venular endothelium. In contrast, exogenous particulates (colloidal carbon) a nd endogenous particulates (erythrocytes, platelets) extravasated fi o m plasma through transendothelial openings. 4. Serial electron microsc opic sections and three-dimensional reconstructions demonstrated that eighty-nine of ninety-two openings were transendothelial pores, not in tercellular gaps. Pore frequency increased 3- to 33-fold when carbon w as used as tracer. 5. The results demonstrate that soluble and particu late tracers extravasate from venules by apparently different transcel lular pathways in response to vasoactive mediators. However, some pore s may derive from rearrangements of VVOs.