Reduction in shear stress, activation of the endothelium, and leukocyte priming are all required for leukocyte passage across the blood-retina barrier

Heping Xu, Ayyakkannu Manivannan, Keith A. Goatman, Hui-Rong Jiang, Janet Liversidge, Peter F. Sharp, John V. Forrester, Isabel J. Crane

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The passage of leukocytes across the blood-retina barrier at the early stages of an inflammatory reaction is influenced by a complex series of interactions about which little is known. In particular, the relationship between hydrodynamic factors, such as shear stress and leukocyte velocity, to the adherence and subsequent extravasation of leukocytes into the retina is unclear. We have used a physiological method, scanning laser ophthalmoscopy, to track labeled leukocytes circulating in the retina, followed by confocal microscopy of retinal flatmounts to detect infiltrating cells at the early stage of experimental autoimmune uveitis. This has shown that retinal vessels are subjected to high shear stress under normal circumstances. During the inflammatory reaction, shear stress in retinal veins is reduced 24 h before leukocyte infiltration. This reduction is negatively correlated with leukocyte rolling and sticking in veins and postcapillary venules, the sites of leukocyte extravasation. Activation of vascular endothelial cells is also a prerequisite for leukocyte rolling and infiltration. In addition, antigen priming of leukocytes is influential at the early stage of inflammation, and this is seen clearly in the reduction in rolling velocity and adherence of the primed leukocytes in activated retinal venules, 9 days postimmunization.

Original languageEnglish
Pages (from-to)224-232
Number of pages9
JournalJournal of Leukocyte Biology
Volume75
Issue number2
DOIs
Publication statusPublished - 29 Feb 2004

Fingerprint

Endothelium
Retina
Leukocytes
Leukocyte Rolling
Venules
Retinal Vein
Ophthalmoscopy
Retinal Vessels
Uveitis
Hydrodynamics
HLA Antigens
Confocal Microscopy
Veins
Lasers
Endothelial Cells
Inflammation

Keywords

  • animals
  • blood-retinal barrier
  • chemotaxis, leukocyte/immunology
  • endothelium, vascular/metabolism
  • female
  • hemorheology
  • leukocytes/immunology
  • mice
  • mice, innbred strains
  • microscopy, confocal
  • retina/immunology
  • retinal vessels/immunology
  • stress, mechanical
  • uveitis/immunology

Cite this

Xu, Heping ; Manivannan, Ayyakkannu ; Goatman, Keith A. ; Jiang, Hui-Rong ; Liversidge, Janet ; Sharp, Peter F. ; Forrester, John V. ; Crane, Isabel J. / Reduction in shear stress, activation of the endothelium, and leukocyte priming are all required for leukocyte passage across the blood-retina barrier. In: Journal of Leukocyte Biology . 2004 ; Vol. 75, No. 2. pp. 224-232.
@article{3b7be7f3407f4341906824056a8f61c4,
title = "Reduction in shear stress, activation of the endothelium, and leukocyte priming are all required for leukocyte passage across the blood-retina barrier",
abstract = "The passage of leukocytes across the blood-retina barrier at the early stages of an inflammatory reaction is influenced by a complex series of interactions about which little is known. In particular, the relationship between hydrodynamic factors, such as shear stress and leukocyte velocity, to the adherence and subsequent extravasation of leukocytes into the retina is unclear. We have used a physiological method, scanning laser ophthalmoscopy, to track labeled leukocytes circulating in the retina, followed by confocal microscopy of retinal flatmounts to detect infiltrating cells at the early stage of experimental autoimmune uveitis. This has shown that retinal vessels are subjected to high shear stress under normal circumstances. During the inflammatory reaction, shear stress in retinal veins is reduced 24 h before leukocyte infiltration. This reduction is negatively correlated with leukocyte rolling and sticking in veins and postcapillary venules, the sites of leukocyte extravasation. Activation of vascular endothelial cells is also a prerequisite for leukocyte rolling and infiltration. In addition, antigen priming of leukocytes is influential at the early stage of inflammation, and this is seen clearly in the reduction in rolling velocity and adherence of the primed leukocytes in activated retinal venules, 9 days postimmunization.",
keywords = "animals, blood-retinal barrier, chemotaxis, leukocyte/immunology, endothelium, vascular/metabolism, female, hemorheology, leukocytes/immunology, mice, mice, innbred strains, microscopy, confocal, retina/immunology, retinal vessels/immunology, stress, mechanical, uveitis/immunology",
author = "Heping Xu and Ayyakkannu Manivannan and Goatman, {Keith A.} and Hui-Rong Jiang and Janet Liversidge and Sharp, {Peter F.} and Forrester, {John V.} and Crane, {Isabel J.}",
year = "2004",
month = "2",
day = "29",
doi = "10.1189/jlb.1002479",
language = "English",
volume = "75",
pages = "224--232",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
number = "2",

}

Reduction in shear stress, activation of the endothelium, and leukocyte priming are all required for leukocyte passage across the blood-retina barrier. / Xu, Heping; Manivannan, Ayyakkannu; Goatman, Keith A.; Jiang, Hui-Rong; Liversidge, Janet; Sharp, Peter F.; Forrester, John V.; Crane, Isabel J.

In: Journal of Leukocyte Biology , Vol. 75, No. 2, 29.02.2004, p. 224-232.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Reduction in shear stress, activation of the endothelium, and leukocyte priming are all required for leukocyte passage across the blood-retina barrier

AU - Xu, Heping

AU - Manivannan, Ayyakkannu

AU - Goatman, Keith A.

AU - Jiang, Hui-Rong

AU - Liversidge, Janet

AU - Sharp, Peter F.

AU - Forrester, John V.

AU - Crane, Isabel J.

PY - 2004/2/29

Y1 - 2004/2/29

N2 - The passage of leukocytes across the blood-retina barrier at the early stages of an inflammatory reaction is influenced by a complex series of interactions about which little is known. In particular, the relationship between hydrodynamic factors, such as shear stress and leukocyte velocity, to the adherence and subsequent extravasation of leukocytes into the retina is unclear. We have used a physiological method, scanning laser ophthalmoscopy, to track labeled leukocytes circulating in the retina, followed by confocal microscopy of retinal flatmounts to detect infiltrating cells at the early stage of experimental autoimmune uveitis. This has shown that retinal vessels are subjected to high shear stress under normal circumstances. During the inflammatory reaction, shear stress in retinal veins is reduced 24 h before leukocyte infiltration. This reduction is negatively correlated with leukocyte rolling and sticking in veins and postcapillary venules, the sites of leukocyte extravasation. Activation of vascular endothelial cells is also a prerequisite for leukocyte rolling and infiltration. In addition, antigen priming of leukocytes is influential at the early stage of inflammation, and this is seen clearly in the reduction in rolling velocity and adherence of the primed leukocytes in activated retinal venules, 9 days postimmunization.

AB - The passage of leukocytes across the blood-retina barrier at the early stages of an inflammatory reaction is influenced by a complex series of interactions about which little is known. In particular, the relationship between hydrodynamic factors, such as shear stress and leukocyte velocity, to the adherence and subsequent extravasation of leukocytes into the retina is unclear. We have used a physiological method, scanning laser ophthalmoscopy, to track labeled leukocytes circulating in the retina, followed by confocal microscopy of retinal flatmounts to detect infiltrating cells at the early stage of experimental autoimmune uveitis. This has shown that retinal vessels are subjected to high shear stress under normal circumstances. During the inflammatory reaction, shear stress in retinal veins is reduced 24 h before leukocyte infiltration. This reduction is negatively correlated with leukocyte rolling and sticking in veins and postcapillary venules, the sites of leukocyte extravasation. Activation of vascular endothelial cells is also a prerequisite for leukocyte rolling and infiltration. In addition, antigen priming of leukocytes is influential at the early stage of inflammation, and this is seen clearly in the reduction in rolling velocity and adherence of the primed leukocytes in activated retinal venules, 9 days postimmunization.

KW - animals

KW - blood-retinal barrier

KW - chemotaxis, leukocyte/immunology

KW - endothelium, vascular/metabolism

KW - female

KW - hemorheology

KW - leukocytes/immunology

KW - mice

KW - mice, innbred strains

KW - microscopy, confocal

KW - retina/immunology

KW - retinal vessels/immunology

KW - stress, mechanical

KW - uveitis/immunology

U2 - 10.1189/jlb.1002479

DO - 10.1189/jlb.1002479

M3 - Article

VL - 75

SP - 224

EP - 232

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 2

ER -