Correlated endothelial caveolin overexpression and increased transcytosis in experimental diabetes.
We investigated the mechanism by which diabetes renders the capillary endothelium more permeable to macromolecules in the lungs of short-term diabetic rats. We used quantitative immunocytochemistry (ICC) to comparatively assess the permeability of alveolar capillaries to serum albumin in diabetic and normoglycemic animals. The effect of diabetes on the population of endothelial caveolae was evaluated by morphometry and by ICC and immunochemical quantification of the amount of caveolin in the whole cell or associated with the purified endothelial plasma membrane. A net increase in the amount of serum albumin taken up by the plasmalemmal vesicles of alveolar endothelial cells and transported to the interstitium was documented in diabetic animals. Interendothelial junctions were not permeated by albumin molecules. The alveolar endothelial cells of hyperglycemic rats contain more caveolae (1.3-fold), accounting for a larger (1.5-fold) fraction of the endothelial volume than those of normal animals. The hypertrophy of the caveolar compartment is accompanied by overexpression of endothelial caveolin 1. Although the aggregated thickness of the endothelial and alveolar epithelium basement membranes increases in diabetes (1.3-fold), the porosity of this structure appears to be unchanged. Capillary hyperpermeability to plasma macromolecules recorded in the early phase of diabetes is explained by an intensification of transendothelial vesicular transport and not by the destabilization of the interendothelial junctions.
Pascariu
Mirela
M
Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montreál, Quebec, Canada.
Bendayan
Moïse
M
Ghitescu
Lucian
L
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D015415:Biomarkers / Q000032:analysis; D002199:Capillary Permeability; D051242:Caveolin 1; D022461:Caveolins / Q000096:biosynthesis*; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D015151:Immunoblotting; D007150:Immunohistochemistry; D011650:Pulmonary Alveoli / Q000098:blood supply; D051381:Rats; D017207:Rats, Sprague-Dawley
D000418:Albumins; D015415:Biomarkers; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins