Zinc transport across an endothelium includes vesicular cotransport with albumin

Bovine pulmonary arterial endothelial cells (BPAEC) were grown on permeable polycarbonate membrane filters suspended between two compartments representing the blood vessel lumen and the interstitium. This in vitro model of an endothelium was subjected to a battery of tests to unravel the mechanisms of zinc transport from the blood into peripheral tissues. Transport of 65Zn across BPAEC from media containing zinc concentrations up to 50 mumol/L exhibited both saturable and nonsaturable kinetics. Vmax of the saturable component was 246 +/- 43 pmol/(h x cm2) and Km was 2.3 +/- 1.3 mumol/L. Transport was pH and temperature sensitive and substantially influenced by albumin and histidine concentrations, but not influenced by analogous minerals or metabolic inhibitors. Inhibition of coated vesicle formation by depletion of intracellular potassium reduced 65Zn transport. Albumin carrying a zinc ion crossed the endothelium more rapidly than zinc-free albumin. When evaluated together, this body of evidence supports the existence of two major pathways of zinc transport across the pulmonary endothelium, but neither involves entry into the endothelial cells. One pathway involves receptor-mediated cotransport with albumin by transcytotic vesicles. The other is nonsaturable and involves cotransport with albumin and low molecular weight ligands, principally histidine, through intercellular junctions and nonselective, bulk-fluid transcytosis.