scholarly journals PERMEABILITY OF INTESTINAL CAPILLARIES

1972 ◽  
Vol 53 (2) ◽  
pp. 365-392 ◽  
Author(s):  
Nicolae Simionescu ◽  
Maia Simionescu ◽  
George E. Palade
Keyword(s):  
Intercellular Junctions ◽  
Liver Glycogen ◽  
Pore System ◽  
Concentration Gradients ◽  
Good Definition ◽  
Plasmalemmal Vesicles ◽  
Tracer Particles ◽  
One Step ◽  
Dynamic Structures ◽  
Capillary Walls

The pathway followed by macromolecules across the wall of visceral capillaries has been studied by using a set of tracers of graded sizes, ranging in diameter from 100 A (ferritin) to 300 A (glycogen). Polysaccharide particles, i.e. dextran 75 (mol wt ∼75,000; diam ∼125 A), dextran 250 (mol wt 250,000; diam ∼225 A), shellfish glycogen (diam ∼200 A) and rabbit liver glycogen (diam ∼300 A), are well tolerated by Wistar-Furth rats and give no vascular reactions ascribable to histamine release. Good definition and high contrast of the tracer particles were obtained in a one-step fixation—in block staining of the tissues by a mixture containing aldehydes, OsO4 and lead citrate in phosphate or arsenate buffer, pH 7.4, followed by lead staining of sections. The glycogens and dextrans used move out of the plasma through the fenestrae and channels of the endothelium relatively fast (3–7 min) and create in the pericapillary spaces transient (2–5 min) concentration gradients centered on the fenestrated sectors of the capillary walls. The tracers also gained access to the plasmalemmal vesicles, first on the blood front and subsequently on the tissue front of the endothelium. The particles are temporarily retained by the basement membrane. No probe moved through the intercellular junctions. It is concluded that, in visceral capillaries, the fenestrae, channels, and plasmalemmal vesicles, viewed as related parts in a system of dynamic structures, are the structural equivalent of the large pore system.

Plasmalemmal vesicles represent the large pore system of continuous microvascular endothelium

1993 ◽  
Vol 265 (2) ◽  
pp. H725-H733 ◽  
Author(s):  
D. Predescu ◽  
G. E. Palade
Keyword(s):  
Intercellular Junctions ◽  
Pore System ◽  
Microvascular Endothelium ◽  
Plasmalemmal Vesicles ◽  
Morphological Studies ◽  
Large Pore ◽  
In Transit

In the capillary physiology literature, molecules and particles larger than 10 nm are assumed to leave the plasma mostly through large pores located at the level of intercellular junctions in microvessels lined with a continuous endothelium. In morphological studies of similar microvessels, outgoing particles > 10 nm were detected in endothelial plasmalemmal vesicles not in intercellular junctions. Because the probes may not be found in transit through the junctions because they may be swept away by strong currents generated by Starling forces, we have examined a large number of junctions in arteriolar, capillary, and venular segments of bipolar vascular fields of mouse diaphragms collected after perfusion with large pore probes. The results presented in this study indicate that 1) the perfused probes accumulate in the luminal introits of the junctions as filtration residues that decrease in size and frequency from arterioles to venules, and 2) large pore probes move across the endothelium exclusively through plasmalemmal vesicles.

scholarly journals PERMEABILITY OF MUSCLE CAPILLARIES TO EXOGENOUS MYOGLOBIN

1973 ◽  
Vol 57 (2) ◽  
pp. 424-452 ◽  
Author(s):  
Nicolae Simionescu ◽  
Maia Simionescu ◽  
George E. Palade
Keyword(s):  
Gel Filtration ◽  
Intercellular Junctions ◽  
Cell Periphery ◽  
Pore System ◽  
Regional Heterogeneity ◽  
Plasmalemmal Vesicles ◽  
Small Pore ◽  
Perinuclear Cytoplasm ◽  
Muscle Capillaries

Whale skeletal muscle myoglobin (mol wt 17,800; molecular dimensions 25 x 34 x 42 Å) was used as a probe molecule for the pore systems of muscle capillaries. Diaphragms of Wistar-Furth rats were fixed in situ at intervals up to 4 h after the intravenous injection of the tracer, and myoglobin was localized in the tissue by a peroxidase reaction. Gel filtration of plasma samples proved that myoglobin molecules remained in circulation in native monomeric form. At 30–35 s postinjection, the tracer marked ∼75% of the plasmalemmal vesicles on the blood front of the endothelium, 15% of those located inside and none of those on the tissue front. At 45 s, the labeling of vesicles in the inner group reached 60% but remained nil for those on the tissue front. Marked vesicles appeared on the latter past 45 s and their frequency increased to ∼80% by 60–75 s, concomitantly with the appearance of myoglobin in the pericapillary spaces. Significant regional heterogeneity in initial labeling was found in the different segments of the endothelium (i.e., perinuclear cytoplasm, organelle region, cell periphery, and parajunctional zone). Up to 60 s, the intercellular junctions and spaces of the endothelium were free of myoglobin reaction product; thereafter, the latter was detected in the distal part of the intercellular spaces in concentration generally equal to or lower than that prevailing in the adjacent pericapillary space. The findings indicate that myoglobin molecules cross the endothelium of muscle capillaries primarily via plasmalemmal vesicles. Since a molecule of this size is supposed to exit through both pore systems, our results confirm the earlier conclusion that the plasmalemmal vesicles represent the large pore system; in addition, they suggest that the same structures are, at least in part, the structural equivalent of the small pore system of this type of capillaries.

scholarly journals Binding and transcytosis of glycoalbumin by the microvascular endothelium of the murine myocardium: evidence that glycoalbumin behaves as a bifunctional ligand.

1988 ◽  
Vol 107 (5) ◽  
pp. 1729-1738 ◽  
Author(s):  
D Predescu ◽  
M Simionescu ◽  
N Simionescu ◽  
G E Palade
Keyword(s):  
Intercellular Junctions ◽  
Concomitant Administration ◽  
Multivesicular Bodies ◽  
Microvascular Endothelium ◽  
Coated Pits ◽  
Gold Complexes ◽  
Plasmalemmal Vesicles ◽  
Bifunctional Ligand ◽  
Albumin Molecule

The binding and transport of glycoalbumin (gA) by the endothelium of murine myocardial microvessels were studied by perfusing in situ 125I-gA or gA-gold complexes (gA-Au) and examining the specimens by radioassays and EM, respectively. After a 3-min perfusion, the uptake of radioiodinated gA is 2.2-fold higher than that of native albumin; it is partially (approximately 55%) competed by either albumin or D-glucose, and almost completely abolished by the concomitant administration of both competitors or by gA. D-mannose and D-galactose are not effective competitors. Unlike albumin-gold complexes that bind restrictively to plasmalemmal vesicles, gA-Au labels the plasma-lemma proper, plasmalemmal vesicles open on the lumen, and most coated pits. Competing albumin prevents gA-Au binding to the membrane of plasmalemmal vesicles, while glucose significantly reduces the ligand binding to plasmalemma proper. Competition with albumin and glucose gives additive effects. Transcytosis of gA-Au, already detected at 3 min, becomes substantial by 30 min. No tracer exit via intercellular junctions was detected. gA-Au progressively accumulates in multivesicular bodies. The results of the binding and competition experiments indicate that the gA behaves as a bifunctional ligand which is recognized by two distinct binding sites: one, located on the plasma membrane, binds as a lectin the glucose residues of gA; whereas the other, confined to plasmalemmal vesicles, recognizes presumably specific domains of the albumin molecule.

scholarly journals INTESTINAL CAPILLARIES

1969 ◽  
Vol 41 (1) ◽  
pp. 33-58 ◽  
Author(s):  
F. Clementi ◽  
G. E. Palade
Keyword(s):  
Electron Microscopy ◽  
Horseradish Peroxidase ◽  
Intestinal Mucosa ◽  
Intercellular Junctions ◽  
Post Injection ◽  
Pore System ◽  
Blood Capillaries ◽  
Large Pore ◽  
Small Pore ◽  
Histochemical Procedure

Horseradish peroxidase (mol. diam. ≃50 A) and ferritin (mol. diam. ≃110 A) were used as probe molecules for the small and large pore system, respectively, in blood capillaries of the intestinal mucosa of the mouse. Peroxidase distribution was followed in time, after intravenous injection, by applying the Graham-Karnovsky histochemical procedure to aldehyde-fixed specimens. The tracer was found to leave the plasma rapidly and to reach the pericapillary spaces 1 min post injection. Between 1 min and 1 min 30 sec, gradients of peroxidase reaction product could be demonstrated regularly around the capillaries; their highs were located opposite the fenestrated parts of the endothelium. These gradients were replaced by even distribution past 1 min 30 sec. Ferritin, followed directly by electron microscopy, appeared in the pericapillary spaces 3–4 min after i.v. injection. Like peroxidase, it initially produced transient gradients with highs opposite the fenestrated parts of the endothelium. For both tracers, there was no evidence of movement through intercellular junctions, and transport by plasmalemmal vesicles appeared less efficient than outflow through fenestrae. It is concluded that, in the blood capillaries of the inintestinal mucosa, the diaphragms of the endothelial fenestrae contain the structural equivalents of the small pore system. The large pore system seems to be restricted to a fraction of the fenestral population which presumably consists of diaphragm-free or diaphragm-deficient units.

Binary Fluid Mixture and Thermocapillary Effects on the Wetting Characteristics of a Heated Curved Meniscus

2003 ◽  
Vol 125 (5) ◽  
pp. 867-874 ◽  
Author(s):  
David M. Pratt ◽  
Kenneth D. Kihm
Keyword(s):  
Pore System ◽  
Concentration Gradients ◽  
Fluid Mixture ◽  
Binary Fluid ◽  
Fluid Mixtures ◽  
Naturally Occurring ◽  
Theoretical Predictions ◽  
Interfacial Temperature ◽  
Binary Fluid Mixtures ◽  
Liquid Vapor

An investigation has been conducted into the interactions of binary fluid mixtures (pentane [C5H12] coolant and decane [C10H22] additive) and thermocapillary effects on a heated, evaporating meniscus formed in a vertical capillary pore system. The experimental results show that adding decane, the secondary fluid that creates the concentration gradient, actually decreases the meniscus height to a certain level, but did increase the sustainable temperature gradient for the liquid-vapor interface, so did the heat transfer rate, delaying the onset of meniscus instability. The results have demonstrated that interfacial thermocapillary stresses arising from liquid-vapor interfacial temperature gradients, which is known to degrade the ability of the liquid to wet the pore, can be counteracted by introducing naturally occurring concentration gradients associated with distillation in binary fluid mixtures. Also theoretical predictions are presented to determine the magnitudes of both the thermocapillary stresses and the distillation-driven capillary stresses, and to estimate the concentration gradients established as a result of the distillation in the heated pore.

Plasmalemmal vesicles function as transcytotic carriers for small proteins in the continuous endothelium

1997 ◽  
Vol 272 (2) ◽  
pp. H937-H949 ◽  
Author(s):  
S. A. Predescu ◽  
D. N. Predescu ◽  
G. E. Palade
Keyword(s):  
Capillary Permeability ◽  
Pore System ◽  
Plasmalemmal Vesicles ◽  
Small Proteins ◽  
Structural Identity ◽  
Heart Perfusion ◽  
Small Pore ◽  
Vesicular Carriers ◽  
Tissue Fractionation

We investigated the location and the structural identity of the small pore system, postulated by the pore theory of capillary permeability, using a murine heart perfusion system and small protein molecules as preferential probes for the small pores. Dinitrophenylated proteins were perfused in situ in the absence and in the presence of N-ethylmaleimide (NEM), a reagent known to interfere with membrane fusion of vesicular carriers with their target membranes. The exit pathways of the tracers from vascular lumina to the interstitia were followed by immunoelectron microscopy and by tissue fractionation biochemistry to quantitate their transport and to estimate the extent of transport inhibition by NEM. After 5 min of perfusion, all tracers used were found essentially restricted to plasmalemmal vesicles (PVs) within the endothelium and NEM inhibited their transport by 80-85%. The transport of [14C]inulin and [14C]sucrose, assumed to follow the paracellular pathway, was marginally affected by NEM. These findings indicate that PVs function as structural equivalents of the small pore system for molecules >2 nm in diameter.

scholarly journals STUDIES ON INFLAMMATION

1961 ◽  
Vol 11 (3) ◽  
pp. 571-605 ◽  
Author(s):  
G. Majno ◽  
G. E. Palade
Keyword(s):  
Endothelial Cells ◽  
Electron Microscope ◽  
Basement Membrane ◽  
Blood Vessels ◽  
Electron Micrographs ◽  
Light Microscope ◽  
Intercellular Junctions ◽  
Supporting Evidence ◽  
Electron Microscopic ◽  
Tracer Particles

The mechanism, whereby histamine and serotonin increase the permeability of blood vessels, was studied in the rat by means of the electron microscope. The drugs were injected subcutaneously into the scrotum, whence they diffused into the underlying (striated) cremaster muscle. An intravenous injection of colloidal HgS was also given, in order to facilitate the identification of leaks by means of visible tracer particles. After intervals varying from 1 minute to 57 days the animals were killed; the cremaster was fixed, embedded in methacrylate, and examined with the electron microscope. One to 12 minutes after the injection, the blood vessels of the smallest caliber (3 to 5 micra as measured on electron micrographs) appeared intact. Numerous endothelial openings were present in blood vessels with a diameter of 7 to 8 micra or more. These gaps were 0.1 to 0.8 micra in width; portions of intercellular junctions were often present in one or both of the margins. The underlying basement membrane was morphologically intact. An accumulation of tracer particles and chylomicra against the basement membrane indicated that the latter behaved as a filter, allowing fluid to escape but retaining and concentrating suspended particulate matter of the size used. Uptake of tracer particles by endothelial vesicles was minimal. Phagocytosis by endothelial cells became more prominent at 3 hours, but as a secondary occurrence; the pericytes were actively phagocytic at all stages. At the 3-hour stage no leaks were found. The changes induced by histamine and serotonin were indistinguishable, except that the latter was more potent on a mole-to-mole basis. In control animals only small accumulations of tracer particles were found in the wall of a number of blood vessels. With regard to the pathogenesis of the endothelial leaks, the electron microscopic findings suggested that the endothelial cells become partially disconnected along the intercellular junctions. Supporting evidence was provided at the level of the light microscope, by demonstrating—in the same preparation—the leaks with appropriate tracer particles1, and the intercellular junctions by the silver nitrate method. The lipid nature of the chylomicron deposits observed in electron micrographs was also confirmed at the level of the light microscope, using cremasters fixed in formalin and stained in toto with sudan red.

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

1978 ◽  
Vol 79 (1) ◽  
pp. 27-44 ◽  
Author(s):  
N Simionescu ◽  
M Simionescu ◽  
G E Palade
Keyword(s):  
Horseradish Peroxidase ◽  
Carbon Black ◽  
Freeze Fracture ◽  
Intercellular Junctions ◽  
Intramembrane Particles ◽  
Size Limit ◽  
Mouse Diaphragm ◽  
Tracer Particles ◽  
Endothelial Junctions ◽  
Venular Endothelium

We have previously established that approximately 30% of the endothelial junctions in the pericytic venules of the mouse diaphragm are open to a gap of approximately 30--60 A, and are fully permeated by hemeundecapeptide (H11P) (mol diam approximately 20 A). 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 approximately 50 A) permeated only approximately 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 A) permeated only a few (less than 5%), and ferritin (mol diam 110 A), 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 approximately 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.

Binary Fluid Mixture and Thermocapillary Effects on the Wetting Characteristics of a Heated Curved Meniscus

2000 ◽  
Author(s):  
David M. Pratt ◽  
Kenneth D. Kihm
Keyword(s):  
Transport Capacity ◽  
Pore System ◽  
Concentration Gradients ◽  
Fluid Mixture ◽  
Binary Fluid ◽  
Fluid Mixtures ◽  
Naturally Occurring ◽  
Interfacial Temperature ◽  
Binary Fluid Mixtures ◽  
Capillary Pore

Abstract An investigation of the thermocapillary effects on a heated, evaporating meniscus formed by binary fluid mixtures of wetting liquids in a vertical capillary pore system has been conducted. Experiments were conducted to primarily observe the wetting characteristics of the binary fluid mixture and how they are affected by the dynamics associated with the heating of and evaporation from a meniscus. The results have demonstrated that interfacial thermocapillary stresses arising from liquid-vapor interfacial temperature gradients that degrade the ability of the liquid to wet the pore can be counteracted by introducing naturally occurring concentration gradients associated with distillation in binary fluid mixtures without affecting the heat transport capacity of the system.

scholarly journals Nonlinear Analyte Concentration Gradients for One-Step Kinetic Analysis Employing Optical Microring Resonators

2012 ◽  
Vol 84 (13) ◽  
pp. 5556-5564 ◽  
Author(s):  
Michael T. Marty ◽  
Courtney D. Kuhnline Sloan ◽  
Ryan C. Bailey ◽  
Stephen G. Sligar
Keyword(s):  
Kinetic Analysis ◽  
Microring Resonators ◽  
Analyte Concentration ◽  
Concentration Gradients ◽  
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