Effects of dextran on lysosomal ultrastructure and protein digestion in renal proximal tubule

Dextrans of different molecular weights, such as dextran T-40 (Rheomacrodex) and dextran T-75 (Macrodex), are often used as plasma substitutes. As a consequence, the influence of dextran on renal function is of much interest. In experimental studies, the tubular transfer maxima for glucose and hippuran [1] were unaffected by infusion of dextran T-40. On the other hand, studies of oliguric or anuric patients who had been infused with large amounts of dextran have revealed in the proximal tubule cells an extensive vacuolization [2–5], which was previously referred to as “osmotic nephrosis” [6]. The vacuoles correspond to endocytic vacuoles and lysosomes, and it has been proposed that dextran is taken up by endocytosis by the proximal tubule cells [7], a proposal which is supported by the histochemical demonstrations of injected dextran in vacuoles of the proximal tubule cells by light [8] and electron microscopy [9, 10].Due to extensive alterations of the lysosomal system, the question has been raised to what extent the absorbed dextran interferes with endocytosis and catabolic functions of the renal tubule lysosomes [11]. The present study, therefore, was undertaken to determine the effect of dextran T-40 on protein uptake, transport, and catabolism in the proximal tubule. Lysozyme labeled with iodine 125 (125I) was used as a tracer because low-molecular-weight proteins, which are filtered in the glomeruli, are taken up by the proximal tubule cells by endocytosis and catabolized by lysosomal enzymes. Protein digestion was determined in renal cortical slices [12] after i.v. injection of the protein into dextran-treated or control rats, and the subcellular localization of dextran was studied after i.v. injection of3H-dextran T-80 by differential centrifugation of renal homogenates

Distribution of the aquaporin CHIP in secretory and resorptive epithelia and capillary endothelia

The existence of water-selective channels has been postulated to explain the high water permeability of erythrocytes and certain epithelial cells. The aquaporin CHIP (channel-forming integral membrane protein of 28 kDa), a molecular water channel, is abundant in erythrocytes and water-permeable segments of the nephron. To determine whether CHIP may mediate transmembrane water movement in other water-permeable epithelia, membranes of multiple organs were studied by immunoblotting, immunohistochemistry, and immunoelectron microscopy using affinity-purified anti-CHIP IgG. The apical membrane of the choroid plexus epithelium was densely stained, implying a role for CHIP in the secretion of cerebrospinal fluid. In the eye, CHIP was abundant in apical and basolateral domains of ciliary epithelium, the site of aqueous humor secretion, and also in lens epithelium and corneal endothelium. CHIP was detected in membranes of hepatic bile ducts and water-resorptive epithelium of gall bladder, suggesting a role in bile secretion and concentration. CHIP was not detected in glandular epithelium of mammary, salivary, or lacrimal glands, suggesting the existence of other water-channel isoforms. CHIP was also not detected within the epithelium of the gastrointestinal mucosa. CHIP was abundant in membranes of intestinal lacteals and continuous capillaries in diverse tissues, including cardiac and skeletal muscle, thus providing a molecular explanation for the known water permeability of certain lymphatics and capillary beds. These studies underscore the hypothesis that CHIP plays a major role in transcellular water movement throughout the body