Cell-specific localization of glucose transporter proteins in mammalian lung

Mammalian lung uses glucose for cellular oxidative metabolism, growth, differentiation, surfactant synthesis, and host defense. Intracellular transport of glucose is accomplished by membrane-associated glycoproteins termed glucose transporters (Gluts). To determine the cell-specific localization patterns, human autopsy lung tissue from preterm (24-32 weeks; n = 4), term infants (38-40 weeks; n = 4), and adults (n = 4) was analyzed for facilitative Glut isoforms and the energy-dependent sodium-glucose cotransporters (SGLT) by Western blot analysis and immunohistochemistry. Antibodies specific for human Glut-1 (erythrocyte, blood-brain barrier type), Glut-3 (brain), Glut-4 (insulin-responsive skeletal muscle/adipocyte), and Glut-5 (kidney/jejunum) were employed. Analysis of Glut-2 (liver/ pancreatic beta-cell/small intestine) was performed in newborn and adult rat lungs, and analysis of SGLT1 (kidney/small intestine) was conducted in newborn and adult rabbit lungs, because of the species specificity of the antirat Glut-2 and antirabbit SGLT1 antibodies employed. In human lung at all ages, our studies;revealed an approximately 45- to 50-kDa Glut-1 protein band in entrapped erythrocytes and perineural sheaths, which serve as a blood-nerve barrier. In the rat lung, an approximately 45-kDa Glut-2 band was seen in the rat bronchial columnar epithelium. Glut-3 was observed in term infant and adult white blood cells and neuroendocrine cells, representing neuronal elements of the autonomic nervous system. Glut-4, Glut-5, and SGLT1 were not detected in lung. We conclude that Gluts are expressed in nonalveolar lung cell types arising from stem cells of the erythroid cell lineage and tissue barrier epithelia (Glut-1), foregut epithelium (Glut-2), myeloid cell lineage (Glut-3), and neuroectoderm (Glut-3). No detectable levels of Glut-4, Glut-5, or SGLT1 Gluts were noted in mammalian lung. The absence of a Glut isoform in the alveolar lining epithelial cells suggests minimal expression of the Glut isoform or the presence of some other transport system, reliance on adjacent cells for substrate supply, or uptake of nonglucose substrate to fuel a relatively low glucose-demanding cellular system.