Ultrastructural changes of lung capillary endothelium in response to botulinum C2 toxin

Ermert, L., H.-R. Duncker, H. Brückner, F. Grimminger,T. Hansen, R. Rössig, K. Aktories, and W. Seeger.Ultrastructural changes of lung capillary endothelium in responseto botulinum C₂ toxin.J. Appl. Physiol. 82(2): 382-388, 1997.The role of the endothelial cytoskeleton for the structuralintegrity of the pulmonary gas exchange area was probed with the use ofClostridium botulinumC₂ toxin. This agent causesselective loss of nonmuscle F-actin. In buffer-perfused rabbit lungs,vascular pressures were kept within physiological ranges. In differentgroups, low-dose [0.3(C_2,I)/0.6(C_2,II) ng/ml] andhigh-dose [10 (C_2,I)/20(C_2,II) ng/ml] toxin wereapplicated into the buffer fluid; experiments were terminated after atotal weight gain of either 1 or 7.5 g. Electron microscopy revealedextensive attenuations, undulations, and protrusions of the endotheliallayer, suggestive of "remodeling" and "flowing" of the cellmembrane in low C₂ toxin-treatedlungs accompanied by few disruptions of the endothelial layer and edema formation. In addition, endothelial cells displayed vesiculation andbleb formation. Lungs that were exposed to high-toxin doses displayedmarked attenuations of the endothelial layer in addition to largeendothelial cell disruptions, which did not include interendothelial junctions. Interestingly, type II epithelial cells displayed fusion oflamellar bodies. Collectively, these data suggest that the actinmicrofilament system is instrumental in supporting endothelial cellmembrane configuration and integrity and maintains the intimal barrierfunction of the lung microvasculature.