Serum albumin decreases transendothelial permeability to macromolecules.
We examined the effects of serum albumin and other serum proteins on the fluxes of tracer 125I-albumin (MW 69 kDa) and 125I-haptoglobin (MW 100 kDa) across the pulmonary artery endothelial monolayer in vitro to test the role of serum proteins in modulating the endothelial barrier function. Replacement of control complete culture medium (20% fetal calf serum in DMEM) with DMEM alone increased the transendothelial 125I-albumin clearance rate (a measure of 125I-albumin permeability) by 83% of the control value. Repletion with 50% calf serum or with 2.0 g% albumin (i.e., the albumin concentration in 50% serum) decreased 125I-albumin permeability to the control value. This effect of serum or albumin was concentration-dependent since neither 12.5% serum nor 0.5 g% albumin (i.e., albumin concentration in 12.5% serum) altered 125I-albumin permeability from control values. The ammonium sulfate-precipitated serum protein fraction rich in albumin decreased 125I-albumin permeability from the control DMEM value, whereas serum fractions containing predominantly gamma-globulin or depleted of protein did not significantly alter 125I-albumin permeability. Other serum proteins that have been proposed to reduce endothelial permeability, alpha 1-acid glycoprotein (0.035-0.14 g/100 ml) and fibronectin (5 mg/100 ml), did not decrease 125I-albumin permeability from DMEM values. The endothelial permeability of 125I-haptoglobin of 4.63 +/- 0.53 x 10(-6) cm/sec in the presence of DMEM was 30% of the 125I-albumin permeability value. The addition of 2.0 g% albumin or 50% serum decreased 125I-haptoglobin permeability to 57 and 31%, respectively, of the DMEM value. These results indicate the critical role of serum albumin in regulating the restrictiveness of the endothelial barrier to macromolecules.
Albany Medical College of Union University, Department of Physiology and Cell Biology, New York 12208.
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Siflinger-Birnboim
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Blumenstock
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Malik
D000818:Animals; D002199:Capillary Permeability; D002417:Cattle; D002460:Cell Line; D004730:Endothelium, Vascular / Q000502:physiology*; D006242:Haptoglobins / Q000378:metabolism; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D008657:Metabolic Clearance Rate; D008833:Microcirculation; D011651:Pulmonary Artery / Q000502:physiology; D012709:Serum Albumin / Q000502:physiology*; D012711:Serum Albumin, Radio-Iodinated / Q000097:blood
D006242:Haptoglobins; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D012709:Serum Albumin; D012711:Serum Albumin, Radio-Iodinated