Shear-Dependent Adhesion of Leukocytes and Lectins to the Endothelium and Concurrent Changes in Thickness of the Glycocalyx of Post-Capillary Venules in the Low-Flow State

Herbert H. Lipowsky, Anne Lescanic

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective: To elucidate shear-dependent effects of deformation of the endothelial glycocalyx on adhesion of circulating ligands in post-capillary venules, and delineate effect of MMPs. Methods: Adhesion of WBCs and lectin-coated FLMs (0.1 μm diameter) to EC of post-capillary venules in mesentery was examined during acute reductions in shear rates (γ·, hemorrhagic hypotension). Adhesion was examined with or without superfusion with 0.5 μm doxycycline to inhibit MMPs. Thickness of the glycocalyx was measured by exclusion of fluorescent 70 kDa dextran from the EC surface. Results: During superfusion with Ringers, rapid reductions in γ· resulted in a significant rise in WBC adhesion and a twofold rise in microsphere adhesion. With addition of doxycycline WBC and FLM adhesion increased twofold under high- and low-flow conditions. FLM adhesion was invariant with γ· throughout the network in the normal (high)-flow state. With reductions in γ·, thickness of the glycocalyx increased significantly, with or without doxycycline. Conclusions: The concurrent increase in WBC and FLM adhesion with increased thickness of the glycocalyx during reductions in shear suggests that glycocalyx core proteins recoil from their deformed steady-state configuration, which increases exposure of binding sites for circulating ligands.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalMicrocirculation
Volume20
Issue number2
DOIs
StatePublished - Feb 1 2013

Fingerprint

Glycocalyx
Venules
Lectins
Endothelium
Leukocytes
Doxycycline
Matrix Metalloproteinases
Ligands
Mesentery
Dextrans
Microspheres
Hypotension
Binding Sites
Proteins

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

@article{e663509980424da5ba012fd8e109dee4,
title = "Shear-Dependent Adhesion of Leukocytes and Lectins to the Endothelium and Concurrent Changes in Thickness of the Glycocalyx of Post-Capillary Venules in the Low-Flow State",
abstract = "Objective: To elucidate shear-dependent effects of deformation of the endothelial glycocalyx on adhesion of circulating ligands in post-capillary venules, and delineate effect of MMPs. Methods: Adhesion of WBCs and lectin-coated FLMs (0.1 μm diameter) to EC of post-capillary venules in mesentery was examined during acute reductions in shear rates (γ·, hemorrhagic hypotension). Adhesion was examined with or without superfusion with 0.5 μm doxycycline to inhibit MMPs. Thickness of the glycocalyx was measured by exclusion of fluorescent 70 kDa dextran from the EC surface. Results: During superfusion with Ringers, rapid reductions in γ· resulted in a significant rise in WBC adhesion and a twofold rise in microsphere adhesion. With addition of doxycycline WBC and FLM adhesion increased twofold under high- and low-flow conditions. FLM adhesion was invariant with γ· throughout the network in the normal (high)-flow state. With reductions in γ·, thickness of the glycocalyx increased significantly, with or without doxycycline. Conclusions: The concurrent increase in WBC and FLM adhesion with increased thickness of the glycocalyx during reductions in shear suggests that glycocalyx core proteins recoil from their deformed steady-state configuration, which increases exposure of binding sites for circulating ligands.",
author = "Lipowsky, {Herbert H.} and Anne Lescanic",
year = "2013",
month = "2",
day = "1",
doi = "10.1111/micc.12013",
language = "English (US)",
volume = "20",
pages = "149--157",
journal = "Microcirculation",
issn = "1073-9688",
publisher = "Wiley-Blackwell",
number = "2",

}

Shear-Dependent Adhesion of Leukocytes and Lectins to the Endothelium and Concurrent Changes in Thickness of the Glycocalyx of Post-Capillary Venules in the Low-Flow State. / Lipowsky, Herbert H.; Lescanic, Anne.

In: Microcirculation, Vol. 20, No. 2, 01.02.2013, p. 149-157.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Shear-Dependent Adhesion of Leukocytes and Lectins to the Endothelium and Concurrent Changes in Thickness of the Glycocalyx of Post-Capillary Venules in the Low-Flow State

AU - Lipowsky, Herbert H.

AU - Lescanic, Anne

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Objective: To elucidate shear-dependent effects of deformation of the endothelial glycocalyx on adhesion of circulating ligands in post-capillary venules, and delineate effect of MMPs. Methods: Adhesion of WBCs and lectin-coated FLMs (0.1 μm diameter) to EC of post-capillary venules in mesentery was examined during acute reductions in shear rates (γ·, hemorrhagic hypotension). Adhesion was examined with or without superfusion with 0.5 μm doxycycline to inhibit MMPs. Thickness of the glycocalyx was measured by exclusion of fluorescent 70 kDa dextran from the EC surface. Results: During superfusion with Ringers, rapid reductions in γ· resulted in a significant rise in WBC adhesion and a twofold rise in microsphere adhesion. With addition of doxycycline WBC and FLM adhesion increased twofold under high- and low-flow conditions. FLM adhesion was invariant with γ· throughout the network in the normal (high)-flow state. With reductions in γ·, thickness of the glycocalyx increased significantly, with or without doxycycline. Conclusions: The concurrent increase in WBC and FLM adhesion with increased thickness of the glycocalyx during reductions in shear suggests that glycocalyx core proteins recoil from their deformed steady-state configuration, which increases exposure of binding sites for circulating ligands.

AB - Objective: To elucidate shear-dependent effects of deformation of the endothelial glycocalyx on adhesion of circulating ligands in post-capillary venules, and delineate effect of MMPs. Methods: Adhesion of WBCs and lectin-coated FLMs (0.1 μm diameter) to EC of post-capillary venules in mesentery was examined during acute reductions in shear rates (γ·, hemorrhagic hypotension). Adhesion was examined with or without superfusion with 0.5 μm doxycycline to inhibit MMPs. Thickness of the glycocalyx was measured by exclusion of fluorescent 70 kDa dextran from the EC surface. Results: During superfusion with Ringers, rapid reductions in γ· resulted in a significant rise in WBC adhesion and a twofold rise in microsphere adhesion. With addition of doxycycline WBC and FLM adhesion increased twofold under high- and low-flow conditions. FLM adhesion was invariant with γ· throughout the network in the normal (high)-flow state. With reductions in γ·, thickness of the glycocalyx increased significantly, with or without doxycycline. Conclusions: The concurrent increase in WBC and FLM adhesion with increased thickness of the glycocalyx during reductions in shear suggests that glycocalyx core proteins recoil from their deformed steady-state configuration, which increases exposure of binding sites for circulating ligands.

UR - http://www.scopus.com/inward/record.url?scp=84873912935&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873912935&partnerID=8YFLogxK

U2 - 10.1111/micc.12013

DO - 10.1111/micc.12013

M3 - Article

C2 - 22963321

AN - SCOPUS:84873912935

VL - 20

SP - 149

EP - 157

JO - Microcirculation

JF - Microcirculation

SN - 1073-9688

IS - 2

ER -