Erythrocyte-derived sphingosine-1-phosphate stabilizes basal hydraulic conductivity and solute permeability in rat microvessels

F. E. Curry, J. F. Clark, R. H. Adamson

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Exogenous sphingosine-1-phosphate (S1P), a lipid mediator in blood, attenuates acute microvascular permeability increases via receptor S1P1 to stabilize the endothelium. To evaluate the contribution of erythrocytes as an endogenous source of S1P to the regulation of basal permeability, we measured permeability coefficients in intact individually perfused venular microvessels of rat mesentery. This strategy also enabled the contributions of other endogenous S1P sources to be evaluated. Apparent permeability coefficients (PS) to albumin and α-lactalbumin and the hydraulic conductivity of mesenteric microvessels were measured in the presence or absence of rat erythrocytes or rat erythrocyte-conditioned perfusate. Rat erythrocytes added to the perfusate were the principal source of S1P in these microvessels. Basal PS to albumin was stable and typical of blood-perfused microvessels (mean 0.5 10× -6 cm/s) when erythrocytes or erythrocyteconditioned perfusates were present. When they were absent, PS to albumin or α-lactalbumin increased up to 40-fold (over 10 min). When exogenous S1P was added to perfusates, permeability returned to levels comparable with those seen in the presence of erythrocytes. Addition of SEW 2871, an agonist specific for S1P1, in the absence of red blood cells reduced PS BSA (40-fold reduction) toward basal. The specific S1P1 receptor antagonist (W-146) reversed the stabilizing action of erythrocytes and increased permeability (27-fold increase) in a manner similar to that seen in the absence of erythrocytes. Erythrocytes are a primary source of S1P that maintains normal venular microvessel permeability. Absence of erythrocytes or conditioned perfusate in in vivo and in vitro models of endothelial barriers elevates basal permeability.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume303
Issue number7
DOIs
StatePublished - Oct 1 2012

Fingerprint

Microvessels
Permeability
Erythrocytes
Lysosphingolipid Receptors
Lactalbumin
Albumins
sphingosine 1-phosphate
Mesentery
Capillary Permeability
Endothelium
Lipids

Keywords

  • Endothelium
  • Erythrocyte
  • Permeability
  • Sphingosine-1-phosphate

ASJC Scopus subject areas

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

Cite this

Erythrocyte-derived sphingosine-1-phosphate stabilizes basal hydraulic conductivity and solute permeability in rat microvessels. / Curry, F. E.; Clark, J. F.; Adamson, R. H.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 303, No. 7, 01.10.2012.

Research output: Contribution to journalArticle

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