Segmental differentiations of cell junctions in the vascular endothelium. The microvasculature.

Simionescu, Maya; Simiónescu, N; Palade, George E.

doi:10.1083/jcb.67.3.863

Cited by 409 publications

(198 citation statements)

References 39 publications

(32 reference statements)

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“…the literature indicate that three types of tight junction can be distinguished on the basis of the morphology of their junctional strands which appear as (a) continuous fibrils, e.g., in the epithelia of the gastro-intestinal tract (11,41), (b) bars, e.g., in the developing junctions (15,28,34) and in the mesothelium (present paper), or (c) rows of particles, e.g., in the arteriolar and capillary endothelium (37,38), stria vascularis (33), and among Sertoli cells (20). Forms transitional from one type to another are, however, occasionally encountered (1,20).…”

Section: S~mnescu and N Si~tonescu Cell Junctions In The Peritonementioning

confidence: 99%

Organization of cell junctions in the peritoneal mesothelium

Simionescu¹,

Simiónescu²

1977

The Journal of Cell Biology

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104

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Intercellular junctions in the mesothelium of the visceral (mesentery and omenturn), and parietal (diaphragm, pre-aortic, and iliac region) peritoneum were examined in rats and mice by using freeze-cleaved preparations. In addition to usual intercellular junctions (cell body junctions), special junctions are found between cell processes and the surface of the neighboring cell (cell process junctions). Cell body junctions are provided with tight junctions and communicating (gap) junctions. The former consist of one to two junctional strands which show a characteristic staggered arrangement, and focal discontinuities. In cell process junctions, the strands form loops or appear as short, free-ending elements; their polymorphism suggests considerable lability, probably in connection with their assembly and disassembly. The existence of free-ending strands indicates that such structures can be used as attachment devices without being concomitantly involved in the formation of occluding zonules. In both types of junctions, the strands can be resolved into bars, -80-100 nm long, frequently provided with terminal enlargements and intercalated particles which occur singly or in small clusters. These particles are morphologically similar to those present in communicating (gap) junctions. The mesothelium is also provided with isolated composite macular junctions. Throughout the mesothelium, the cleavage plane follows the outer contour of junctional strands and particles, suggesting that strand-to-strand interactions in the apposed membranes are weaker than interactions between each strand and underlying cytoplasmic structures. In their general geometry and cleavage characteristics, the mesothelial junctions resemble the junctions found in the venular endothelium.Earlier interest in the mechanisms of transport of solutes (3,5,6,8,21,9,32), particulate material (12, 10, 16), and cells across the mesothelium has been recently renewed after the success of peritoneal dialysis as a maintenance technique in chronically uremic patients (7, 23). Despite past investigations, current views concerning the structural substrate of the high permeability of the mesothelial membrane are still markedly divergent. According to a number of studies, water-soluble toolecules cross the mesothelium by passive diffusion presumably along intercellular junctions (5, 21,9, 12, 13, 10), whereas according to other investigations transport across the mesothelium is an active process (35, 32) effected primarily via vesicles (30,42,19,17). These divergent views have broader implications than are immediately apparent, since it has been postulated that the mesothelium, due to its being morphologically and functionally similar to the vascular endothelium, can

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Section: S~mnescu and N Si~tonescu Cell Junctions In The Peritonementioning

confidence: 99%

Organization of cell junctions in the peritoneal mesothelium

Simionescu¹,

Simiónescu²

1977

The Journal of Cell Biology

Self Cite

104

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“…After an additional 15-to 20-min immersion in the same fixative, the specimens were treated for 2 h at 4~ with 25% glycerol in 0.1 M HCINa cacodylate buffer, pH 7.2-7.4. Tissue fragments were then placed on metal carriers and further processed for freeze-fracturing as previously described (22,10). 12 mice were used for this study; from the BMFs chosen, 34 replicas were prepared on which 86 endothelial junctions were examined.…”

Section: Freeze-fracture Preparationsmentioning

confidence: 99%

“…To get further insight into the morphological and functional characteristics of the intercellular junctions of the venular endothelium, experiments were carried out to determine: (a) the size limit of permeant molecules; (b) the intramembranous organization of these venular junctions as compared to that observed in other vascular beds (22); and (c) their sensitivity to histamine and 5-hydroxytryptamine (5-HT). In other locations (cremaster [13,14], bronchioles [17], mesentery [19], cheek pouch [29,30]) these and other mediators are known to cause focal separations of the endothelial cells in the postcapillary venules.…”

mentioning

confidence: 99%

Open junctions in the endothelium of the postcapillary venules of the diaphragm.

Simiónescu¹,

Simionescu²,

Palade³

1978

The Journal of Cell Biology

Self Cite

167

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We have previously established that -30% of the endothelial junctions in the pericytic venules of the mouse diaphragm are open to a gap of -30-60 ,~, and are fully permeated by hemeundecapeptide (HllP) (mol diam -20 /~). To estimate the size limit for molecules that can permeate these junctions, we have administered graded tracers intravenously and studied their behavior at the level of pericytic venules in bipolar microvascular fields (BMFs) in the mouse diaphragm. Horseradish peroxidase (HRP) (mol diam -50 A) permeated only -50% of the open junctions of the venular endothelium. Outflow through venular junctions appeared to be modest since the tracer remained restricted to the perivenular spaces. Hemoglobin (Hb, mol diam 64 x 55 x 50/~) permeated only a few (<5%), and ferritin (mol diam 110 /~), practically none, of the endothelial junctions of the pericytic venules. The findings suggest that under normal conditions the size limit for permeant molecules for open venular junctions is -60 A. Replicas of freeze-fracture preparations from appropriate regions in BMF showed that the intercellular junctions of the venular endothelium have the same organization as previously described for the corresponding segments of the microvasculature in the omentum and mesentery: discontinuous creases or grooves either free of or marked by few intramembrane particles only. Administration of histamine (topically or systemically) and 5-hydroxytryptamine (5-HT) (topically) resulted in typical focal separations of the endothelial junctions and intramural deposits of large tracer particles (carbon black) in the postcapillary venules.

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“…The structural heterogeneity consists in the number of caveolae (that is highest in capillaries) and their generated channels, the presence of fenestrae with diaphragms (in visceral capillaries) or lacking diaphragms (in kidney glomeruli and liver sinusoidal capillaries), and the complexity of interendothelial junctions that are more elaborate in arterial than in venular segments of the vasculature. 8,9 In addition, variations exist in the frequency of Weibel Palade bodies' (lowest in microvessels) capacity to participate in neovascularization, which is characteristic for capillary and venular EC (expressing vascular endothelial growth factor receptors), 10 the response to shear stress, 11 and the distribution of surface enzymes and frequency of membrane receptors. The latter can be schematically classified in receptors for vasoactive molecules, endocytotic receptors (including scavenger receptors), and transcytotic receptors.…”

mentioning

confidence: 99%

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

Simionescu¹

2007

ATVB

224

150

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Abstract-By location, between the blood and tissues and the multiple functions, the endothelial cells (ECs) play a major role in securing body homeostasis. The ECs sense all variations occurring in the plasma and interstitial fluid, and respond (function of intensity), initially by modulation of their constitutive functions, then by dysfunction, expressed by temporarily altered functions and a phenotypic shift, and ultimately by injury/death. In dyslipidemia/hyperglycemia, the initial response of EC is the modulation of 2 constitutive functions: permeability and biosynthesis. Increased transcytosis of plasma ␤-lipoproteins leads to their accumulation within the hyperplasic basal lamina, interaction with matrix proteins, and conversion to modified and reassembled lipoproteins (MRL). This generates a multipart inflammatory process and EC dysfunction characterized by expression of new cell adhesion molecules and MCP-1 that trigger T-lymphocytes and monocyte recruitment, diapedesis, and homing within the subendothelium where activated macrophages become foam cells. The latter, together with the subendothelial accrual of MRL, growth factors, cytokines, and chemokines, and accretion of smooth muscle cells of various sources lead to atheroma formation; in advanced disease, the EC overlaying atheroma take up lipids, become EC-derived foam cells, and the cytotoxic ambient ultimately conducts to EC apoptosis. Understanding the mechanisms of EC dysfunction is a prerequisite for EC-targeted therapy to reduce the incidence of cardiovascular diseases.

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Segmental differentiations of cell junctions in the vascular endothelium. The microvasculature.

Abstract: Small vascular units consisting of an arteriole, its capillaries, and the emerging venule (ACV units) were identified in the rat omentum and mesentery. They were fixed in situ and processed for electron microscopy either as whole units or as dissected segments.

Cited by 409 publications

References 39 publications

Organization of cell junctions in the peritoneal mesothelium

Organization of cell junctions in the peritoneal mesothelium

Open junctions in the endothelium of the postcapillary venules of the diaphragm.

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

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