Correlation of permeability with the structure of the endothelial layer of pulmonary artery intimal explants.
Changes in vascular permeability are associated with structural damage to endothelial cells. These functional and structural changes can be produced experimentally and examined by using intimal explants from bovine pulmonary artery. Correlation of functional with structural changes allows us to dissect the mechanisms responsible for endothelial damage. We have shown that incubation of intimal explants with histamine causes transient formation of interendothelial dilatations and an increased rate of equilibration of tritiated water and [14C]sucrose across the intimal explant. Exposure to endotoxin also causes interendothelial dilatations but the endothelial damage is more severe than that with histamine, and in vivo experiments show a more prolonged increase in pulmonary vascular permeability. Leukocyte migration has also been suggested to result in a decreased barrier function of the endothelial layer. Experiments with the endothelial layer of intimal explants and separated bovine leukocytes suggest that transendothelial migration may depend on the chemotactic stimulus. Neither granulocyte migration toward zymosan-activated plasma nor lymphocyte migration toward lymphocyte-conditioned medium (RPMI in which lymphocytes were incubated with concanavalin A) leads to detectable increases in explant permeability, but granulocyte migration toward lymphocyte-conditioned medium does result in increased equilibration of [14C]sucrose. Finally, a theoretical model has been used to examine the permeability changes seen for the intimal explants exposed to histamine. The model consists of two compartments with radioactive tracers diffusing across a filter of known permeability. Such a model gives good agreement with data obtained in intact sheep, indicating that mathematical models allow quantitative estimates of barrier function in intimal explants that compare favorably with in vivo data.
Meyrick
B
B
Perkett
E A
EA
Harris
T R
TR
Brigham
K L
KL
D000818:Animals; D002463:Cell Membrane Permeability; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004727:Endothelium / Q000166:cytology* / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D007365:Intercellular Junctions / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology*; D015054:Zymosan / Q000494:pharmacology
D004731:Endotoxins; D006632:Histamine; D015054:Zymosan