Structural and transport property alterations of the lung capillary endothelium in diabetes.
There are reports that lung function is altered in diabetes mellitus. Since data are limited concerning the structural--functional correlates in hyperglycemic animals, we designed experiments to assess: (i) whether hyperglycemia induces changes in the structure of the lung capillary endothelial cells (EC), and (ii) the effect of advanced glycation endproducts of albumin (AGE-Alb) on EC. Experiments were conducted on mice and hamsters rendered diabetics by streptozotocin (D-STZ) injection; age-matched animals were used as controls (C). The structure of EC, and the interaction of EC with AGE-Alb adsorbed to 5 nm colloidal gold (AGE-Alb.Au) were examined by electron microscopy; the uptake and cellular distribution of [125I]-AGE-Alb were investigated by spectrometry and autoradiography. The results showed that, compared to C group, in D-STZ animals the alveolar capillary EC exhibited: (i) an uneven distribution of the anionic sites exposed by the luminal plasmalemma, (ii) a metabolicaly active phenotype, (iii) a thickened basal lamina provided with focal nodules, similar in density and distribution to those found in the glomerular basal lamina in diabetes; in addition, (iv) a narrowed or collapsed lumen was found in approximately 30% of the capillaries. The functional alterations of lung EC in diabetes consisted in increased uptake of intravascularly infused [125I]-AGE-Alb and enhanced transcytosis and endocytosis of AGE-Alb.Au. The fusion of plasmalemmal vesicles, and opening of the interendothelial junctions observed, may account for the increased permeability of the alveolar capillary EC. This study asserts that hyperglycemia affects the structure and functional properties of the alveolar capillary EC, and suggests the existence of microangiopathic alterations in diabetic lung.
Popov
D
D
Institute of Cellular Biology and Pathology N. Simionescu, Bucharest, Romania. popov@simionescu.instcellbiopath.ro
Simionescu
M
M
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000503:physiopathology*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology* / Q000648:ultrastructure*; D017127:Glycation End Products, Advanced / Q000097:blood; D006943:Hyperglycemia / Q000139:chemically induced / Q000503:physiopathology; D008168:Lung / Q000098:blood supply* / Q000473:pathology* / Q000648:ultrastructure; D008171:Lung Diseases / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D012039:Regional Blood Flow / Q000502:physiology*; D012709:Serum Albumin / Q000378:metabolism; D014316:Tritium
D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D014316:Tritium