Permeability of muscle capillaries to small heme-peptides. Evidence for the existence of patent transendothelial channels.

Abstract

Two heme-peptides (HP) of about 20-A diameter (heme-undecapeptide [HI IP], mol wt ~ 1900 and heme-octapeptide [H8P], mol wt ~1550), obtained by enzymic hydrolysis of cytochrome c, were used as probe molecules in muscle capillaries (rat diaphragm). They were localized in situ by a peroxidase reaction, enhanced by the addition of imidazole to the incubation medium. Chromatography of plasma samples showed that HPs circulate predominantly as monomers for the duration of the experiments and are bound by aldehyde fixatives to plasma proteins to the extent of ~50% (H8P) to ~95% (HI IP). Both tracers cross the endothelium primarily via plasmalemmal vesicles which become progressively labeled (by reaction product) from the blood front to the tissue front of the endothelium, in three successive resolvable phases. By the end of each phase the extent of labeling reaches > 90% of the corresponding vesicle population. Labeled vesicles appear as either isolated units or chains which form patent channels across the endothelium. The patency of these channels was checked by specimen tilting and graphic analysis of their images. No evidence was found for early or preferential marking of the intercellular junctions and spaces by reaction product. It is concluded that the channels are the most likely candidate for structural equivalents of the small pores of the capillary wall since they are continuous, water-filled passages, and are provided with one or more strictures of < 100 A. Their frequency remains to be established by future work.

Recombinant Expression of Caveolin-1 in Oncogenically Transformed Cells Abrogates Anchorage-independent Growth

“…Samples were examined under a JEOL transmission electron microscope and photographed at a magnification of ϫ 25,000 (30,35). Caveolae were identified by their characteristic flask-shape, size (50 -100 nm), and location at or near the plasma membrane (1)(2)(3)(4).…”

“…Morphologically, they appear as 50 -100 nm vesicular structures near or attached to the plasma membrane (3,4). Although caveolae are present in most cell types, they are most abundant in terminally differentiated cells such as adipocytes, endothelial cells, type I pneumocytes, and skeletal muscle cells (reviewed in Ref.…”

Temperature dependence of protein transport across lymphatic endothelium in vitro.

“…Thus Bundgaard et al (8) prefer the term "endothelial plasmalemmal invaginations" . At this stage it remains to be seen whether invaginations from opposite surfaces join to form transendothelial channels, as first described by Simionescu et al (34), or whether they pinch off from one surface before opening to the other as suggested by the membrane staining technique (18). If transendothelial channels exist, transport by diffusion is likely.…”

Implications of Early Structural-Functional Changes in the Endothelium for Vascular Disease

“…Biologists discovered that the ECs are endowed with few copies of all cellular organelles including clathrin-coated pits and vesicles, but as characteristic feature they are gifted with an unusually high number of plasmalemmal vesicles, 1 now termed caveolae, transendothelial channels made up of one or more vesicles fused simultaneously to both EC fronts, 2 specific storage granules, the Weibel-Palade bodies, 3 and differentiated microdomains on the plasmalemma. 4 As social cells, they establish homotypic and heterotypic intercellular junctions that connect ECs one to another or to neighboring subjacent cells: pericytes in capillaries and postcapillary venules and smooth muscle cells (SMCs) in arterioles and large vessels.…”