Colloidal gold particles as a new in vivo marker of early acute lung injury

Abstract

Permeability of the endothelial barrier to large molecules plays a pivotal role in the manifestation of early acute lung injury. We present a novel and sensitive technique that brings microanatomical visualization and quantification of microvascular permeability in line. White New Zealand rabbits were anesthetized and ventilated mechanically. Rabbit serum albumin (RSA) was labeled with colloidal gold particles. We quantified macromolecular leakage of gold-labeled RSA and thickening of the gas exchange distance by electron microscopy, taking into account morphology of microvessels. The control group receiving a saline solution represented a normal gas exchange barrier without extravasation of gold-labeled albumin. Infusion of lipopolysaccharide (LPS) resulted in a significant displacement of gold-labeled albumin into pulmonary cells, the lung interstitium, and even the alveolar space. Correspondingly, intravital fluorescence microscopy and digital image analysis indicated thickening of width of alveolar septa. The findings were accompanied by a deterioration of alveolo-arterial oxygen difference, whereas wet/dry ratio and albumin concentration in the bronchoalveolar lavage fluid failed to detect that early stage of pulmonary edema. Inhibition of the nuclear enzyme poly(ADP-ribose) synthetase by 3-aminobenzamide prevented LPS-induced microvascular injury. To summarize: colloidal gold particles visualized by standard electron microscopy are a new and very sensitive in vivo marker of microvascular permeability in early acute lung injury. This technique enabling detailed microanatomical and quantitative pathophysiological characterization of edema formation can form the basis for evaluating novel treatment strategies against acute lung injury.

RETRACTED: Nanoparticle-Assisted Ultrasound for Cancer Therapy

“…In addition to thermal effects, [12] the ultrasound radiation is known to produce mechanical pressure that results in acoustic streaming and cavitation within cellular systems. [13] Free cavitation bubbles are formed in a liquid media when the local liquid pressure drops below the saturated vapor pressure at the rarefaction period of the propagated ultrasound wave.…”

Toxico-/biokinetics of nanomaterials

“…After i.v. administration of albumin-coated gold NP to rodents, receptor-mediated transcytosis via caveolae (50-100-nm caveolin-1-coated vesicles, formed from indentations of the cell membrane) was observed (Heckel et al 2004). In the lung, during inspiratory expansion and expiratory contraction of the alveoli, caveolae with openings around 40 nm disappear and reappear, forming vesicles thought to transport macromolecules across the cells.…”

Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery

“…It was documented in the lung [45] and myocardium [46] that the increased vascular permeability induced by inflammatory stimulations was due to the enhanced transendothelial traffic, which was carried out by a population of cytoplasm vesicles. In line with these findings, the result of electron microscopy in the present study showed that the number of vesicles in cytoplasm of endothelial cells of venules was increased apparently by LPS continuous infusion, whereas the endothelial cells themselves and the intercellular junctions remained intact, implying that the LPS-induced albumin leakage observed in the present situation was accomplished by the transendothelial route.…”