Development of protein drug delivery system from the lung based on ligand recognition mechanisms of the receptors

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The purpose of this study is to obtain the information for the development of protein drug delivery system from the lung. I examined the uptake of FITC-1abeled albumin and insulin by alveolar type II epithelial cells using cultured RLE-6TN cells as well as primary cultured alveolar type II cells isolated from rats.1. FITC-Albumin uptake by RLE-6TN cells was temperature-, concentration-, and energy-dependent. The uptake was mediated by high-affinity and low-affinity systems, and the former system was found to be the clathrin-mediated endocytosis.2. The uptake of FITC-insulin by RLE-6TN cells was partly mediated by the clathrin-mediated endocytosis, but other systems would also be involved.3. The fate of FITC-albumin and insulin taken up by RLE-6TN cells was examined. These proteins were partly localized in lysosomes, and gradually degraded over time.4. Ligand blot analysis showed that there were some possible receptor proteins for albumin in the plasma membranes of RLE-6TN cells.5. FITC-Albumin uptake by primary cultured alveolar type II cells isolated from rats was shown to be mediated by the clathrin-mediated endocytosis, like the uptake in RLE-6TN cells.Further studies concerning the activities of protein drug uptake by alveolar type II and I cells, related receptors, the mechanisms of ligand recognition by the receptors would help to develop new strategies for protein drug delivery system from the lung.