title: Fibrin contact increases endothelial permeability to albumin.
abstract: We studied the effects of contact of bovine pulmonary artery endothelial cell monolayers with fibrin on the endothelial barrier function. Fibrin formed by clotting purified fibrinogen (0.5 to 3.0 mg/ml) with alpha-thrombin (1 U/ml) was added to endothelial monolayers and permeability measurements were made after fibrin removal. Fibrin incubation for 3 hours resulted in 2- to 5-fold increases in transendothelial 125I-albumin permeability. Permeability returned to baseline value within 3 hours after fibrin removal. Direct contact with fibrin was necessary for the response, since fibrin separated from the endothelium did not increase permeability. Contact with agarose (2 mg/ml) or fibrinogen (0.5 to 3.0 mg/ml) also did not increase endothelial permeability. Transmission electron microscopic examination indicated normal appearance of interendothelial junctions at a time when albumin permeability was increased and no overt evidence of endothelial injury. Incubation of fibrin with endothelial monolayers at 4 degrees C prevented the increase in albumin permeability. We examined the possibility that increased albumin transcytosis was responsible for fibrin's effect using 14C-sucrose (Mr = 342D), a lipid insoluble tracer. Fibrin increased sucrose flux by 1.5-fold compared to 2- to 5-fold increases in albumin flux. The results indicate that fibrin contact with the endothelial cell increases endothelial permeability. The effect of fibrin may involve activation of temperature-sensitive bulk phase transcytosis of albumin.
authors.affiliation: Department of Physiology, Albany Medical College of Union University, New York 12208.
authors.forename: S K
authors.initials: SK
authors.lastname: Lo
authors.forename: P J
authors.initials: PJ
authors.lastname: Del Vecchio
authors.forename: H
authors.initials: H
authors.lastname: Lum
authors.forename: A B
authors.initials: AB
authors.lastname: Malik
mesh_terms: D000418:Albumins / Q000493:pharmacokinetics*; D000818:Animals; D002250:Carbon Radioisotopes; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D005337:Fibrin / Q000502:physiology*; D007457:Iodine Radioisotopes; D008854:Microscopy, Electron; D013395:Sucrose / Q000493:pharmacokinetics; D013696:Temperature; D013997:Time Factors
chemical_list: D000418:Albumins; D002250:Carbon Radioisotopes; D007457:Iodine Radioisotopes; D013395:Sucrose; D005337:Fibrin