A model for interpreting the tracer labeling of interendothelial clefts

Bingmei Fu, Fitz Roy E Curry, Roger H. Adamson, Sheldon Weinbaum

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

We extended the model describing the low molecular weight electron dense tracer wake in the interendothelial cleft and surrounding tissue to describe the time-dependent transport of intermediate size solutes of 1.0-3.5 nm radius by convection and diffusion in an interendothelial cleft containing a fiber matrix. This model provides a quantitative basis on which to reinterpret electron microscopic studies of the distribution of tracers such as horseradish peroxidase (HRP; molecular weight=40,000; Stokes radius =3.0 nm) along the interendothelial cell cleft from the lumen to the tissue for example, we show that, in contrast to our results with low molecular weight tracers, the wake of large molecular weight tracers on the abluminal side of the junctional strand is not likely to be detected, because the concentration of the tracer is predicted to be very low in most experiments. Thus the lack of a tracer such as HRP on the abluminal side of the junctional strand and in the tissue is not as strong evidence against the presence of a cleft pathway as suggested previously. The model does provide the basis for the design of experiments to locate both the principal molecular sieve and breaks in the junctional strand from the standing gradient on the luminal side of the junctional strand. An important experimental variable is the pressure in the vessel lumen which can be varied between 0 and 30 cm H2O to change the contributions of diffusive and convective transport to transcapillary exchange through the interendothelial cleft. This approach will also allow the testing of models for transcapillary pathways for large molecules by measuring the distribution of fluorescent tracers across the microvessel wall and in the tissue surrounding the microvessel using confocal microscopy.

Original languageEnglish (US)
Pages (from-to)375-397
Number of pages23
JournalAnnals of Biomedical Engineering
Volume25
Issue number2
DOIs
StatePublished - Mar 1997

Fingerprint

Labeling
Molecular weight
Tissue
Electrons
Confocal microscopy
Molecular sieves
Design of experiments
Molecules
Fibers
Testing
Experiments

Keywords

  • Fiber matrix
  • Frog mesenteric capillary
  • High molecular weight tracers
  • Junction strand
  • Ultrafiltration

ASJC Scopus subject areas

  • Biomedical Engineering

Cite this

A model for interpreting the tracer labeling of interendothelial clefts. / Fu, Bingmei; Curry, Fitz Roy E; Adamson, Roger H.; Weinbaum, Sheldon.

In: Annals of Biomedical Engineering, Vol. 25, No. 2, 03.1997, p. 375-397.

Research output: Contribution to journalArticle

Fu, Bingmei ; Curry, Fitz Roy E ; Adamson, Roger H. ; Weinbaum, Sheldon. / A model for interpreting the tracer labeling of interendothelial clefts. In: Annals of Biomedical Engineering. 1997 ; Vol. 25, No. 2. pp. 375-397.
@article{b1e034bab413495288a484f029758b40,
title = "A model for interpreting the tracer labeling of interendothelial clefts",
abstract = "We extended the model describing the low molecular weight electron dense tracer wake in the interendothelial cleft and surrounding tissue to describe the time-dependent transport of intermediate size solutes of 1.0-3.5 nm radius by convection and diffusion in an interendothelial cleft containing a fiber matrix. This model provides a quantitative basis on which to reinterpret electron microscopic studies of the distribution of tracers such as horseradish peroxidase (HRP; molecular weight=40,000; Stokes radius =3.0 nm) along the interendothelial cell cleft from the lumen to the tissue for example, we show that, in contrast to our results with low molecular weight tracers, the wake of large molecular weight tracers on the abluminal side of the junctional strand is not likely to be detected, because the concentration of the tracer is predicted to be very low in most experiments. Thus the lack of a tracer such as HRP on the abluminal side of the junctional strand and in the tissue is not as strong evidence against the presence of a cleft pathway as suggested previously. The model does provide the basis for the design of experiments to locate both the principal molecular sieve and breaks in the junctional strand from the standing gradient on the luminal side of the junctional strand. An important experimental variable is the pressure in the vessel lumen which can be varied between 0 and 30 cm H2O to change the contributions of diffusive and convective transport to transcapillary exchange through the interendothelial cleft. This approach will also allow the testing of models for transcapillary pathways for large molecules by measuring the distribution of fluorescent tracers across the microvessel wall and in the tissue surrounding the microvessel using confocal microscopy.",
keywords = "Fiber matrix, Frog mesenteric capillary, High molecular weight tracers, Junction strand, Ultrafiltration",
author = "Bingmei Fu and Curry, {Fitz Roy E} and Adamson, {Roger H.} and Sheldon Weinbaum",
year = "1997",
month = "3",
doi = "10.1007/BF02648050",
language = "English (US)",
volume = "25",
pages = "375--397",
journal = "Annals of Biomedical Engineering",
issn = "0090-6964",
publisher = "Springer Netherlands",
number = "2",

}

TY - JOUR

T1 - A model for interpreting the tracer labeling of interendothelial clefts

AU - Fu, Bingmei

AU - Curry, Fitz Roy E

AU - Adamson, Roger H.

AU - Weinbaum, Sheldon

PY - 1997/3

Y1 - 1997/3

N2 - We extended the model describing the low molecular weight electron dense tracer wake in the interendothelial cleft and surrounding tissue to describe the time-dependent transport of intermediate size solutes of 1.0-3.5 nm radius by convection and diffusion in an interendothelial cleft containing a fiber matrix. This model provides a quantitative basis on which to reinterpret electron microscopic studies of the distribution of tracers such as horseradish peroxidase (HRP; molecular weight=40,000; Stokes radius =3.0 nm) along the interendothelial cell cleft from the lumen to the tissue for example, we show that, in contrast to our results with low molecular weight tracers, the wake of large molecular weight tracers on the abluminal side of the junctional strand is not likely to be detected, because the concentration of the tracer is predicted to be very low in most experiments. Thus the lack of a tracer such as HRP on the abluminal side of the junctional strand and in the tissue is not as strong evidence against the presence of a cleft pathway as suggested previously. The model does provide the basis for the design of experiments to locate both the principal molecular sieve and breaks in the junctional strand from the standing gradient on the luminal side of the junctional strand. An important experimental variable is the pressure in the vessel lumen which can be varied between 0 and 30 cm H2O to change the contributions of diffusive and convective transport to transcapillary exchange through the interendothelial cleft. This approach will also allow the testing of models for transcapillary pathways for large molecules by measuring the distribution of fluorescent tracers across the microvessel wall and in the tissue surrounding the microvessel using confocal microscopy.

AB - We extended the model describing the low molecular weight electron dense tracer wake in the interendothelial cleft and surrounding tissue to describe the time-dependent transport of intermediate size solutes of 1.0-3.5 nm radius by convection and diffusion in an interendothelial cleft containing a fiber matrix. This model provides a quantitative basis on which to reinterpret electron microscopic studies of the distribution of tracers such as horseradish peroxidase (HRP; molecular weight=40,000; Stokes radius =3.0 nm) along the interendothelial cell cleft from the lumen to the tissue for example, we show that, in contrast to our results with low molecular weight tracers, the wake of large molecular weight tracers on the abluminal side of the junctional strand is not likely to be detected, because the concentration of the tracer is predicted to be very low in most experiments. Thus the lack of a tracer such as HRP on the abluminal side of the junctional strand and in the tissue is not as strong evidence against the presence of a cleft pathway as suggested previously. The model does provide the basis for the design of experiments to locate both the principal molecular sieve and breaks in the junctional strand from the standing gradient on the luminal side of the junctional strand. An important experimental variable is the pressure in the vessel lumen which can be varied between 0 and 30 cm H2O to change the contributions of diffusive and convective transport to transcapillary exchange through the interendothelial cleft. This approach will also allow the testing of models for transcapillary pathways for large molecules by measuring the distribution of fluorescent tracers across the microvessel wall and in the tissue surrounding the microvessel using confocal microscopy.

KW - Fiber matrix

KW - Frog mesenteric capillary

KW - High molecular weight tracers

KW - Junction strand

KW - Ultrafiltration

UR - http://www.scopus.com/inward/record.url?scp=0031106072&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031106072&partnerID=8YFLogxK

U2 - 10.1007/BF02648050

DO - 10.1007/BF02648050

M3 - Article

C2 - 9084841

AN - SCOPUS:0031106072

VL - 25

SP - 375

EP - 397

JO - Annals of Biomedical Engineering

JF - Annals of Biomedical Engineering

SN - 0090-6964

IS - 2

ER -