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C C Michel

Publications and source records attributed to C C Michel.

At least 55 records · Page 3Linked to original sources
PubMed1988

Inflammatory changes in permeability and ultrastructure of single vessels in the frog mesenteric microcirculation.

1. In fifteen experiments, single microvessels in the exposed mesenteries of pithed frogs were perfused with Ringer solutions containing bovine serum albumin (40 mg ml-1). For each vessel, the hydraulic permeability of its walls (Lp) and effective osmotic pressure exerted across them (sigma delta pi) were determined from measurements of fluid filtration rates at two capillary pressures (Michel, Mason, Curry, Tooke & Hunter, 1974) before and at predetermined times after the tissue temperature had been raised abruptly from approximately 15 degrees C to 30-35 degrees C. Temperatures greater than 30 degrees C appear to damage the tissues of frogs acclimatized to temperatures of 5-10 degrees C. 2. In fourteen out of fifteen experiments Lp rose when the temperature was raised to 30-35 degrees C. In twelve of these experiments the increase in Lp was greater than expected from the fall in water viscosity with temperature, and was progressive. In five vessels where measurements were made 1-2 min after tissue temperature was raised, Lp increased from an initial mean value (+/- S.E.M.) of 3.76 (+/- 0.54) x 10(-3) micron s-1 cmH2O-1 to one of 8.72 (+/- 1.68) x 10(-3) micron s-1 cmH2O-1. In nine vessels where measurements were made at 10 min after tissue temperature was raised, Lp increased from an initial mean value of 4.03 (+/- 0.72) x 10(-3) micron s-1 cmH2O-1 to one of 16.9 (+/- 3.5) x 10(-3) micron s-1 cmH2O-1. Further increases in Lp were seen at 15 and 20 min. 3. The changes in the effective osmotic pressure opposing filtration, sigma delta pi, were very variable. Out of the twelve vessels which showed large changes in Lp with tissue heating, four showed no reduction in sigma delta pi after 10 min, though sigma delta pi fell in three of these vessels at 15 min. In the other eight vessels, sigma delta pi fell as Lp rose. A quantitative theory developed in this paper allowed the changes in sigma delta pi to be analysed in terms of a component across the regions of vessel wall of increased permeability (sigma H delta pi H) and a component across regions where Lp was unchanged. In six vessels sigma H delta pi H approximated to zero; in two vessels sigma H delta pi H was 6.2 and 4.5 cmH2O.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Quantitative comparisons of hydraulic permeability and endothelial intercellular cleft dimensions in single frog capillaries.

1. We have investigated the ultrastructure of the intercellular clefts of the walls of single capillaries and venules of the frog mesentery in which the hydraulic permeability (Lp) and the reflection coefficient of the vessel walls to serum albumin (sigma BSA) had been measured using the micro-occlusion technique of Michel (1980). Our aim was to investigate whether the dimensions of the clefts were sufficient to accommodate the pathways through the vessel walls necessary to account for the measured permeability. 2. Lp was measured in seventeen individually perfused vessels. The walls of fourteen of these were relatively impermeable to macromolecules with a sigma to albumin greater than 0.66 (mean value 0.83, S.E.M. +/- 0.04). The Lp of these fourteen vessels ranged from 1.8 x 10(-7) to 12.5 x 10(-7) cm s-1 cmH2O-1 and had a mean value of 5.9 (S.E.M. +/- 0.85) x 10(-7) cm s-1 cmH2O-1. 3. Cleft dimensions estimated from electron micrographs of 642 transversely sectioned endothelial cell junctions from the same seventeen vessels gave a value for the mean cleft width (W) of 0.0220 micron (S.E.M. +/- 0.0064 micron). The mean depth of the clefts from luminal to abluminal surface of the endothelium (delta x) was 0.395 micron (S.E.M. +/- 0.091 micron) with a range of 0.104-1.70 micron. The cleft length per unit area of cell wall (L), calculated using the formulation of Bundgaard & Frøkjaer-Jensen (1982), was 2064 (S.E.M. +/- 112) cm cm-2. Measurements were also made of cleft dimensions from longitudinally sectioned junctions from five of the seventeen vessels. 4. The fraction of the surface area of capillary wall occupied by the clefts (Ap = LW) had a mean value of 0.0048 (+/- 0.00014) for all seventeen vessels with a range of 0.0030-0.0074 when estimated from transverse sections. There was no correlation between the variation of Lp between different vessels and the variations of Ap. 5. Data from the fourteen vessels when sigma BSA was greater than 0.66 revealed a correlation between values of Lp and the reciprocal of delta x (r = 0.6675, P less than 0.01). No correlation was found between Lp and the mean thickness of the endothelial cells in the vicinity of the clefts. This is strong evidence for the intercellular cleft being the principal pathway for fluid movements. Variation in cleft depth appears to be a factor determining variation in permeability between different capillaries.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Effect of albumin on the osmotic pressure exerted by myoglobin across capillary walls in frog mesentery.

1. Individual capillaries in mesenteries of pithed frogs were perfused sequentially with two frog Ringer solutions containing myoglobin at a concentration of 70 mg/ml. The first perfusate solution contained bovine serum albumin at a concentration of 10 mg/ml. The second perfusate contained no albumin. The modified Landis micro-occlusion technique (Michel, Mason, Curry & Tooke, 1974) was used to measure the capillary hydraulic conductivity and the effective osmotic pressure of the myoglobin solution across the capillary wall under conditions where the transcapillary concentration difference was established by steady-state ultrafiltration. 2. In six capillaries the effective osmotic pressure of the myoglobin solution at 20-22 degrees C was 15.9 +/- 2.2 (S.E. of mean) cmH2O when albumin was in the perfusate and 10.1 +/- 1.1 cmH2O after albumin was removed from the perfusate. 3. The hydraulic conductivity of the capillary wall increased from a mean value of 6.5 +/- 1.4 X 10(-7) cm/(s cmH2O) when albumin was in the perfusate to 15.6 +/- 3.8 X 10(-7) cm/(s cmH2O) during perfusion with Ringer solution containing myoglobin alone. 4. Control experiments to measure steady-state filtration rates at pressures 10-30 cmH2O were carried out to check the assumption in the method that the reduction in the measured osmotic pressure of myoglobin was the result of changes in the properties of the molecular sieve within the capillary wall and was not simply the result of solute accumulation on the tissue side of the capillary wall. 5. The measured reduction in the effective osmotic pressure of myoglobin when albumin was removed from the perfusate does not conform to the hypothesis (Crone, 1984) that the tight segment of the intercellular junction is the principal molecular filter for myoglobin in the wall of frog mesenteric capillaries. 6. Our results do conform to the hypothesis that a network of fibrous molecules, reinforced by adsorbed albumin, forms the principal molecular filter at the capillary wall in frog mesenteric capillaries.

Albumins↗
PubMed1987

Steady-state fluid filtration at different capillary pressures in perfused frog mesenteric capillaries.

1. The theory of steady-state filtration through capillary walls (Michel, 1984) has been developed and investigated in experiments on single capillaries of the frog mesentery perfused with Ringer solutions containing bovine serum albumin (BSA) and Ficoll 70. 2. In each experiment, the micro-occlusion technique of Michel, Mason, Curry, Tooke & Hunter (1974) has been used to investigate the relation between fluid movements per unit area of capillary wall (Jv/A) and capillary pressure (Pc) under two sets of conditions in the same vessel. First, the relation has been determined following brief perfusions, where the difference in oncotic pressure across the capillary wall approximated to the perfusate oncotic pressure at all values of Pc. These results are referred to as the transient data. Secondly, the relation was investigated by estimating Jv/A at values of Pc which had been maintained constant during at least 2 min of perfusion prior to the measurement. Under these conditions the concentration of macromolecules in the pericapillary fluid was determined by the steady-state composition of the filtrate passing through the capillary wall, and these results are referred to as steady-state data. 3. In all fifteen capillaries investigated, the relationship between Jv/A and Pc was linear for the transient data and conspicuously non-linear in the steady state. When Pc exceeded the oncotic pressure of the perfusate, steady-state values for Jv/A lay slightly above but parallel to the transient values for the same vessel. At values of Pc less than the perfusate oncotic pressure, the transient data showed reabsorption of fluid from the tissues, but in the steady state either fluid movements were so small as to be undetected or slight filtration was observed. The steady-state data followed the pattern predicted by theory. 4. The transient data were used to estimate the reflection coefficient of the capillary wall (sigma) to the macromolecular solute. In seven vessels, the mean sigma to BSA was 0.76 (S.E. of mean +/- 0.04) and in eight different vessels mean sigma to Ficoll 70 in the presence of BSA (10 mg ml-1) was 0.98 (S.E. of mean +/- 0.05). The steady-state data were consistent with the prediction that the oncotic pressure opposing high filtration rates approximates to sigma 2 pi c in the steady state, where pi c is the perfusate oncotic pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

The effects of chemical fixation on the permeability of frog mesenteric capillaries.

1. We have investigated the effects on microvascular permeability of two chemical fixatives, glutaraldehyde/formaldehyde mixture and osmium tetroxide, both of which are used widely in electron microscopy. 2. The permeability of single perfused frog mesenteric capillaries was assessed using the technique of Michel (1980) to estimate the hydraulic conductance (Lp) of the vessel walls and the effective osmotic pressure (sigma delta pi) which could be exerted across them by the neutral macromolecule, Ficoll 70. 3. In each experiment, Lp and sigma delta pi were estimated in the same capillary before and after chemical fixation with either an aldehyde mixture (n = 6) or 1% osmium tetroxide (n = 6). In the absence of serum proteins in the perfusate, the values of Lp recorded prior to fixation were high. The effect of both fixatives was to reduce Lp. With aldehydes the mean value (+/- S.E.M.) of Lp fell from 22.1 (+/- 6.3) x 10(-3) to 5.7 (+/- 2.0) x 10(-3) microns s-1 cmH2O-1. With osmium tetroxide the mean Lp fell from 29.1 (+/- 8.5) x 10(-3) to 8.6 (+/- 3.6) x 10(-3) microns s-1 cmH2O-1. 4. The perfusates contained the neutral macromolecule, Ficoll 70, at a concentration of 60 mg ml-1 which exerted an osmotic pressure of 35 cmH2O in a membrane osmometer. In the absence of plasma proteins in the perfusate, sigma delta pi was only a fraction of this perfusate oncotic pressure prior to fixation. After aldehyde treatment there was a small but insignificant decrease in sigma delta pi. Osmium tetroxide, however, increased sigma delta pi from a mean (+/- S.E.M.) of 6.3 (+/- 1.6) cmH2O before fixation to 16.4 (+/- 2.8) cmH2O after fixation, P less than 0.01 using a paired t test. 5. In three experiments, the reflection coefficient of the capillary wall to NaCl sigma NaCl, was measured using the technique of Curry, Mason & Michel (1976) before and after osmium fixation. Fixation raised sigma NaCl from a mean value (+/- S.E.M.) of 0.009 (+/- 0.001) to one of 0.017 (+/- 0.004). Although these changes may be interpreted as an increase in the contribution to the total Lp of the capillary wall of channels which are available only to water, the changes are too small for such a mechanism to account for the increase in reflection coefficient to Ficoll 70. 6. The reduction in Lp following chemical fixation could represent an increase in the hydraulic resistance of either the capillary wall itself, or in the tissues surrounding the vessel.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Haemoconcentration and accumulation of white cells in the feet during venous stasis.

In experiments on eight healthy human subjects changes in the composition of the venous blood leaving the foot were examined during a 45-min period of sitting. Each subject reclined for 30-min before sitting with the foot approximately 1 m below the heart. Fluid filtration from the plasma into the tissues during sitting raised the haematocrit from an initial value of 41 +/- 0.6% to 49 +/- 1% after 20-min and to 51 +/- 1.5% at 40-min. The corresponding increase in plasma protein concentration was from 6.5 +/- 0.1 gdl-1 to 8.0 +/- 0.2 gdl-1 after 20 min and to 9.0 +/- 0.3 gdl after 40-min of sitting. Plasminogen activator levels in the foot venous blood during sitting were raised two to three fold over those found in venous blood taken from the arm at the start of the experiment. By contrast, after 20 min of sitting, white cell count of the venous blood of the foot was unchanged from the initial value of 7.4 +/- 0.8 X 10(-9) l-1 and increased to only 7.8 +/- 0.9 X 10(-9) l-1 at 40-min. This was in spite of an increase in the number of circulating white cells which, in blood taken from the arm at 45-min, had risen to 8.3 +/- 0.8 X 10(-9) l-1. The venous blood leaving the feet also failed to show an increase in platelet numbers. It is argued that approximately 15-20% of the white cells entering the feet during quiet sitting, do not leave in the venous blood. The possible significance of the results to the pathophysiology of venous hypertension is discussed.

Adult↗
PubMed1985

The effects of bovine serum albumin and a form of cationised ferritin upon the molecular selectivity of the walls of single frog capillaries.

Single frog mesenteric capillaries have been perfused with Ringer solutions containing the neutral macromolecule Ficoll 70 at a concentration of 40 mg ml-1, while the tissues have been washed with Ringer solution containing no macromolecules but otherwise of similar composition. The effective osmotic pressures (sigma delta II) set up across the capillary wall by the Ficoll 70 were used to assess the wall's molecular selectivity. The hydraulic conductivities, Lp, of the capillary walls were also measured. In seven capillaries the addition of bovine serum albumin (BSA) to the perfusate at concentrations of 1 and 10 mg ml-1 increased sigma delta II from a mean value of 7.14 +/- 1.81 cm H2O to one of 18.71 +/- 2.33 cm H2O and at the same time halved Lp. In another eight capillaries, the addition of a form of cationised ferritin (CF) to the perfusate at a concentration of 1 mg ml-1 increased sigma delta II from a mean value of 5.69 +/- 0.87 cm H2O to one of 16.69 +/- 0.262 cm H2O and reduced Lp to between a third and a half of its original value. In a further seven capillaries, the addition of native ferritin at a concentration of 1 mg ml-1 to the perfusate had no effect on either sigma delta II or Lp. It is suggested that both CF and BSA increase the reflection coefficients of capillary walls to Ficoll 70 by binding to the surface coat of the endothelium. The results are discussed in terms of a development of the fiber matrix theory of Curry and Michel (1980).

Animals↗
PubMed1985

The effects of native and modified bovine serum albumin on the permeability of frog mesenteric capillaries.

Single capillaries in the mesenteries of pithed frogs were perfused sequentially with two frog Ringer solutions. The first solution contained no protein; the second solution contained either native or chemically modified bovine serum albumin (BSA) at a concentration of 3-5 mg ml-1. During each perfusion capillary permeability was assessed from the hydraulic conductivity of the capillary wall (Lp) which was determined from measurements of fluid filtration rate at two or more different capillary pressures (Michel, Mason, Curry, Tooke & Hunter, 1974). Lp measured during perfusion with protein-free Ringer solution was on average three times greater than its value for the same vessel perfused with Ringer solution containing native BSA. This confirms the findings of Mason, Curry & Michel (1977). BSA, which had been succinylated to modify the free amino groups of its lysine residues, appeared to be as effective as native BSA in reducing Lp. After modification of its arginine side chains by exposure to 1,2-cyclohexanedione (CHD) in the presence of 0.2 M-NaOH, BSA lost its property of reducing Lp in capillaries perfused with Ringer solution. Exposure of BSA to 0.2 M-NaOH followed by dialysis against normal Ringer solution did not affect its property of reducing Lp. CHD-treated BSA at a concentration of 2.5 mg ml-1 had no effect upon the effective osmotic pressure exerted across capillary walls by Ringer perfusates containing the neutral polymer Ficoll 70 at a concentration of 40 mg ml-1. Native BSA raised the effective osmotic pressure from 7.07 +/- 1.93 cmH2O to 20.50 +/- 2.37 cmH2O (n = 7; P less than 0.001). It is concluded that the effects of BSA on permeability depend upon specific sites in the BSA molecule. It is suggested that these sites involve positively charged arginine side chains of the albumin molecule. The results are discussed in terms of the fibre-matrix hypothesis of capillary permeability and in terms of Brown's (1976) theory for the structure of albumin.

Animals↗
PubMed1985

The Malpighi lecture. Vascular permeability--the consequence of Malpighi's hypothesis.

The permeability of microvessels to water and small hydrophilic solutes varies considerably between different vascular beds and even between individual vessels in the same vascular bed. Provided the tissues are undamaged, the filtering properties of vessel walls to macromolecules are relatively constant and an analysis of the variations in hydraulic conductances and permeabilities to small ions between different endothelia suggests that the channels for hydrophilic molecules are similar in a wide range of vessels. In undamaged tissues, variations in permeability may be accounted for by variations in the frequency of channels per unit area of vessel wall. The permeability of vessel walls to water and small hydrophilic molecules and their ability to sieve macromolecules are consistent with the molecular filter being a lattice of fibrous molecules which covers and fills the channels through the endothelium. Direct and indirect evidence indicate that globular proteins are part of the molecular filter and it is suggested that they bind the fibrous molecules into a more uniform lattice (the fibre matrix) which greatly increases its selectivity. The question of how the contraction of adjacent endothelial cells might widen the intercellular clefts and thus regulate permeability is discussed. Preliminary experiments show that the permeability of frog capillaries can be varied by varying concentrations of Mg2+ (rather than Ca2+) in the presence of the ionophore A23187 and suggest an interesting line of investigation.

Animals↗
PubMed1983

The effects of cationised ferritin and native ferritin upon the filtration coefficient of single frog capillaries. Evidence that proteins in the endothelial cell coat influence permeability.

To investigate whether certain macromolecules reduce capillary permeability by binding to the surface coat of endothelial cells, the effects of cationised ferritin (CF) upon the filtration coefficient (Lp) of individually perfused frog mesenteric capillaries were compared with those of native ferritin (NF). With perfusate CF concentrations between 0.1 g 100 ml-1 and 2.5 g 100 ml-1, Lp was reduced to approximately 30% of its value for the same vessel perfused with protein-free Ringer solution. Electron micrographs of the perfused capillaries revealed that over this range of perfusate concentrations. CF was concentrated uniformly in the endothelial cell coat, occupying 8.5% of its volume. Neither the effect of cationised ferritin upon Lp nor its concentration in the cell coat varied significantly over this range of perfusate concentrations. When perfusate concentration of CF was reduced to 0.01 g 100 ml-1, CF no longer reduced Lp and its concentration in the cell coat fell below 2%. Native ferritin, which is excluded from the cell coat, did not reduce Lp at a perfusate concentration of 0.1 g 100 ml-1. At a concentration of 2.5 g 100 ml-1, NF reduced Lp in a few very permeable vessels (Lp greater than 60 X 10(-3) microns sec-1 cm H2O-1) but had no significant effect on vessels with lower and more normal values of Lp. The effects of CF upon Lp can be described in terms of the Kozeny equation if a major proportion of the hydraulic resistance through the capillary wall is attributed to a fiber protein matrix.

Animals↗
PubMed1982

The effects of temperature on ferritin transport by endothelial cell vesicles in the capillaries of the frog mesentery.

Using electron microscopy we have determined the appearance of ferritin in the endothelial cell vesicles of frog mesenteric capillaries after varying periods of exposure of the luminal surface of the cell to a ferritin solution, at 17-20 degrees C and at 4-7 degrees C. At 17-20 degrees C, the pattern of labelling observed in the absence of flow through the capillary is very similar to that previously described by us in continuously perfused capillaries [1]. Some vesicles are labelled after the shortest exposures (less than 1 sec) and labelling increases with exposure to reach steady values at 40-60 s. At 4-6 degrees C, a similar initial level of labelling is observed. There is, however, no further increase in labelling as the period of exposure is increased. The effect of temperature on the uptake and transfer of ferritin by the endothelial cell vesicles is consistent with our previous view. We suggest that the cavities of the rapidly labelling vesicles communicate directly with the capillary lumen [1], and their labelling should be unaffected at low temperatures. The secondary, slow rise in labelling, we suggested, resulted from fusions of adjacent vesicles and we would expect this process to be abolished at low temperature.

Animals↗
PubMed1981

The role of vesicles in the transport of ferritin through frog endothelium.

1. The transport of ferritin molecules by endothelial cell vesicles has been quantitatively investigated by electron microscopy. Single mesenteric capillaries of pithed frogs were perfused with solutions containing 6.7 g ferritin 100 ml.-1 for known periods before fixation in situ with osmium tetroxide. 2. Two series of experiments were carried out: in the first series the perfusate contained bovine serum albumin (1.0 g 100 ml.-1); in the second series the perfusate contained no protein other than the ferritin. To assess the molecular radius of ferritin in solution, the free diffusion coefficient of ferritin was measured in the presence and absence of albumin. 3. The free diffusion coefficient of ferritin in saline solution (110 m-mole 1.-1) was found to be 0.35 X 10(-6) cm2 sec-1 at 21 degrees C and was not affected by the presence of bovine serum albumin. This indicates that there is no significant binding of albumin to ferritin in solution and yields a value for the Stokes-Einstein radius of ferritin of 6.1 nm. 4. In all perfusion experiments the percentage of luminal vesicles containing ferritin exceeded the percentage of labelled cytoplasmic vesicles, which in turn exceeded the percentage of labelled abluminal vesicles. 5. Labelling of all vesicle populations was seen after perfusions lasting less than 1 sec. At this time luminal vesicles were more heavily labelled in the absence of albumin. 6. The labelling of luminal vesicles increased with lengthening perfusion times up to 30-40 sec, after which steady levels of labelling were achieved. The rate of rise in luminal labelling and the steady-state levels reached were both greater in the absence of albumin. By contrast cytoplasmic labelling increased above its initial value only after perfusions of longer than 10 sec. 7. In the steady state, labelled cytoplasmic vesicles contained, on average, fewer ferritin molecules than labelled luminal vesicles. This finding is inconsistent with translocation of labelled luminal vesicles across the cell. 8. It is suggested that the early constant labelling of cytoplasmic and abluminal vesicles is consistent with the existence of vesicular channels. Later cytoplasmic labelling may result from the transient fusion of cytoplasmic vesicles with labelled luminal vesicles for periods long enough to allow mixing of vesicular contents. Albumin may affect vesicular transport by its interaction with the endothelial glycocalyx.

Animals↗
PubMed1980

Filtration coefficients and osmotic reflexion coefficients of the walls of single frog mesenteric capillaries.

1. Single capillaries in the mesentery of pithed frogs were perfused with frog Ringer solutions containing various concentrations of bovine serum albumin and myoglobin. Filtration coefficients (Lp) of the capillary wall were determined from measurements of fluid filtration rate at a series of different capillary pressures (Michel, Mason, Curry & Tooke, 1974). The osmotic reflexion coefficients (sigma) to albumin and myoglobin were determined by comparing the effective osmotic pressure exerted by these solutes across the capillary walls with their osmotic pressures in a membrane osmometer. 2. Lp and sigma to albumin were measured in eighteen vessels at different sites in the capillary bed with the tissue temperature in the range of 20-24 degrees C. Lp varied from 1.5 x 10(-3) to 15 x 10(-3) micrometer sec-1 cm H2O-1 having a higher mean value in nine venous capillaries (11.33 x 10(-3) micrometer sec-1 cm H2O-1) than in nine arterial and mid-capillaries (4.83 x 10(-3) micrometer sec-1 cm H2O-1). For all eighteen vessels sigma to albumin had a mean value of 0.816 (S.E. of mean +/- 0.027). There was no correlation between Lp and sigma. The mean value of sigma for the venous capillaries was 0.841 (S.E. of mean +/- 0.04) and the other nine vessels 0.802 (S.E. of mean +/- 0.034). 3. The osmotic reflexion coefficient to myoglobin was measured in seven different capillaries and found to have a mean value of 0.348 (S.E. of mean +/- 0.012) at 20-24 degrees C. The Lp of the capillaries varied from 3.0 x 10(-3) to 10.5 x 10(-3) micrometer sec-1 cm H2O-1. There was no correlation between sigma for myoglobin and Lp. 4. The method of Curry, Mason & Michel (1976) was used to measure sigma for urea in eight capillaries at 20-24 degrees C (sigma for albumin was also measured in two of these vessels). The mean value of sigma for urea was 0.061 (S.E. of mean +/- 0.012). The exclusive water channel (Curry et al. 1976) was calculated to have a value of 0.209 x 10(-3) micrometer sec-1 H2O-1. 5. The effects of temperature on Lp were investigated in a further seven capillaries. It was found that when tissue temperature changed slowly (less than 2 degrees C min-1) the changes of Lp were similar to the reciprocal changes in the viscosity of water. 6. The estimates of Lp and sigma for myoglobin and serum albumin are discussed in terms of the classical pore theory and in terms of a theory that the molecular sieving properties of the capillary wall reside in a matrix of molecular fibres which covers the endothelial cells and fills the channels through or between them. A quantitative theory of a fibre matrix membrane is given in the Appendix.

Animals↗
PubMed1979

The ultrastructure of frog mesenteric capillaries of known filtration coefficient.

The capillaries of the frog mesentery were investigated by transmission electronmicroscopy. The mean diameter of these vessels was 20 micrometers and a single layer of five to six endothelial cells (on average) contributed to each circumference. Their ultrastructure was very similar to that of mammalian capillaries of the continuous type [Bennett, Luft and Hampton, 1959]. The endotherlial cells, which contained many vesicles, were joined by specialized junctions and surrounded by a continuous basement membrane. Eleven capillaries were examined after the filtration coefficient of their walls had been investigated by the microperfusion micro-occlusion technique of Michel, Mason, Curry and Tooke [1974]. No abnormal appearances were observed even after the vessels had been perfused with protein free solutions which have been shown to increase filtration coefficient five fold. No morphological differences between capillaries were seen to accompany large differences in the filtration coefficients.

Animals↗
PubMed1979

The labelling of vesicles in frog endothelial cells with ferritin.

1. The labelling of endothelial cell vesicles with ferritin has been investigated by electron microscopy. Single capillaries in the frog mesentery have been perfused with solutions of known concentrations of ferritin for known periods before fixing the tissue in situ by superfusion with osmium tetroxide. 2. At 17 degrees C, the percentage of lumenal vesicles labelled with ferritin increased as the period of perfusion was increased up to 16 sec prior to fixation. When perfusions were longer than 16 sec, the percentage of vesicles labelled with ferritin remained fairly constant at 70%. 3. At 3 degrees C, no more than 25% of the lumenal vesicles were labelled during the first 30 sec. 4. After correcting the data for losses of ferritin due to sectioning, the distribution of ferritin molecules in the lumenal vesicles was consistent with a Poisson distribution. 5. After perfusions of 16 sec or longer, the number of ferritin molecules per labelled vesicle was roughly three to four times less than would be predicted from the lumenal concentration. 6. At all times there was a gradient of vesicles labelled with ferritin across the endothelial cells, i.e. the percentage of lumenal vesicles labelled was greater than that for cytoplasmic vesicles which in turn was greater than that for vesicles at the ablumenal surface. 7. Whereas the labelling of lumenal vesicles from zero time up to 16-20 sec, the main increase in labelling of cytoplasmic vesicles occurred between 10 and 20 sec. 8. It is concluded that there is a major diffusion barrier to ferritin molecules either close to the endothelial cell surface or across the necks of the lumenal vesicles. It also appears that ferritin molecules do not have access to vesicles during the latter part of their residence at the lumenal surface.

Animals↗