The bloodless rat: a new model for macromolecular transport studies across lung endothelium

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Abstract
To examine the effect of circulating proteins on the passage of i.v. injected native ferritin across pulmonary capillary endothelium, rats were exchange transfused with FC-43 fluorocarbon emulsion (FCE) [Fluosol-43] under ether anesthesia. Protein concentration was reduced to < 1.1 mg/ml by exchange transufusion, followed by FCE containing 15, 30 or 60 mg/ml of lyophilized rat serum protein (LRSP). Two minutes after ferritin injection, lungs were prepared for ultrastructural morphometry. The diameter and numerical density of vesicles remained unchanged under all experimental conditions; however at 0.6 mg/ml of circulating protein there was a 5- and 10-fold increase, respectively, in percent vesicle (%VL) and basement membrane labeling (BML) by ferritin. This was reversible; at 60 mg/ml of circulating protein %VL and BML was indistinguishable from controls. Following a reduction of circulating protein to < 1.1 mg/ml, the addition of 15 mg/ml LRSP reduced %VL but had no effect on BML. In addition to shuttling vesicles there may be a 2nd mechanism for the transport of ferritin, possibly involving transendothelial chains of vesicles.