While it is an established fact that histamine and serotonin increase the permeability of blood vessels, the exact portion of the vascular tree which is so affected has not been conclusively demonstrated. The present study was undertaken to clarify this point.Our experiments were based on a method to which we refer as "vascular labeling," and which permits one to identify leaking vessels by means of visible accumulations of foreign particles within their walls. The mechanism of the labeling, elucidated by previous electron microscopic studies, is the following. Histamine and serotonin cause the endothelial cells of certain vessels to separate, and thus to create discrete intercellular gaps. Plasma escapes through these gaps, and filters through the basement membrane. If the plasma has been previously loaded (by intravenous injection) with colloidal particles of a black material such as carbon or mercuric sulfide, these particles--too large to pass through the basement membrane--will be retained and accumulate in visible amounts within the wall of the leaking vessel. This method is used to maximal advantage if the tissue is cleared and examined by transillumination in toto, so that leaking vessels can be accurately identified in their relationship to the vascular tree.As a test tissue we used the rat cremaster, a laminar striated muscle which can be easily excised with its vascular supply virtually intact. The rats were prepared with an intravenous injection of carbon or HgS, and a subcutaneous injection into the scrotum of histamine, serotonin, or NaC1 (as a control). The injected drug diffused into the underlying cremastcr and the vessels became labeled. One hour later, when the carbon had been cleared from the blood stream, the animal was killed. The cremaster was excised, stretched, fixed in formalin, cleared in glycerin, and examined by transillumination under a light microscope.The lesions induced by histamine and serotonin were identical. The leaking vessels, as indicated by the carbon deposits, always belonged to the venous side of the circulation. The heaviest deposits were found in venules 20 to 30 micra in diameter. The deposits decreased towards larger venules up to a maximum diameter of 75 to 80 micra, and towards the finer vessels until the caliber reached approximately 7 micra. Essentially spared by the deposits were the finest vessels, 4 to 7 micra in diameter, and constituting an extensive network oriented along the muscular fibers.By killing animals at varying intervals after the injections, it was found that the carbon particles were slowly removed from the vascular walls by the action of phagocytic cells. After 10 months there was still enough carbon locally to be recognized by the naked eye.

No abstract

An electron microscope study was made of the mode of lymphocyte migration across the endothelial layer of venules in the Peyer's patches of mice and rats. Single and serial sections were examined. Of a total of about 800 lymphocytes observed in single sections, 91% were located between endothelial cells and 9% were surrounded by endothelial cytoplasm in the particular plane of section. 62% of the lymphocytes occurred in groups of two or more. In long sequences of serial sections through 21 endothelial cells, all lymphocytes were located external to the endothelial cells though some appeared "internal" at certain levels of sectioning. The probability that a lymphocyte which appears to be surrounded by endothelial cell cytoplasm actually lies within the cell was analyzed with a mathematical model derived from data obtained from single sections. The results of this analysis suggested that at least 93–99% of lymphocytes (within 90% limits of confidence) take an intercellular path in their migration from blood to lymph. It is concluded that lymphocytes migrate across the vascular endothelium by insinuating themselves between endothelial cells and not by passing through them. Rather than constituting an increased barrier to cell migration, the unusual height of the endothelial cells in these vessels is interpreted to be a special adaptation which allows sustained cell traffic without excessive fluid loss taking place concomitantly.

No abstract

The topographic distribution of blood vessels in Peyer's patches of mice was studied by light and scanning electron microscopy with whole mounts of flattened gut segments and vascular corrosion casts. Peyer's patches are imbedded in the intestinal wall and share its blood supply. Two to four mural trunks may contribute to the area of the patch. In and around the lymphoid nodules the microcirculation is highly specialized. The nodule is permeated by a meshwork of fine capillaries that is supplied by arterioles entering on the serosal and lateral surfaces. Blood flow to the lymphoid nodule appears to be monitored by arterial sphincters; the dense lymphatic tissue can also be bypassed by arteriovenous communications. An extensive venous network encircles the nodule. Most of these venules are lined by high endothelium which is penetrated by lymphocytes. The geometry of these vessels suggests a slow and turbulent flow in these vascular segments that may aid margination of lymphocytes. A planar capillary plexus lies subjacent to the mucosal epithelium in the dome area.