Differential role of actin in lung endothelial and epithelial barrier properties in perfused rabbit lungs

Abstract

D Di if ff fe er re en nt ti ia al l r ro ol le e o of f a ac ct ti in n i in n l lu un ng g e en nd do ot th he el li ia al l a an nd d e ep pi it th he el li ia al l b ba ar rr ri ie er r p pr ro op pe er rt ti ie es s i in n p pe er rf fu us se ed d r ra ab bb bi it t l lu un ng gs s L. Ermert* + , R. Rössig*, T. Hansen*, H. Schütte*, K. Aktories**, W. Seeger* ABSTRACT: Lung fluid balance is critically dependent on capillary endothelial and alveolar epithelial barrier properties, and cytoskeletal components have been implicated in these barrier functions. In an earlier study, we perfused Clostridium botulinum C 2 toxin, which effects selective loss of non-muscle F-actin, through isolated rabbit lungs: a severalfold increase in the capillary filtration coefficient (Kfc) was noted, together with attenuations and disruptions of endothelial cells upon electron microscopic examination. In this model we have investigated the influence of the C 2 toxin on alveolar epithelial barrier properties. Epithelial permeability was assessed by continuous monitoring of the transepithelial passage of technetiumlabelled diethylenetriamine penta-acetic acid ( 99m Tc-DTPA), offered to the alveolar surface by aerosol technique.Intravascular administration of hydrogen peroxide, used as control agent, was shown to provoke a four-to fivefold increase in the clearance rate of 99m Tc-DTPA under conditions of severe fluid leakage into the lung interstitial and alveolar space. Intravascular administration of C 2 toxin caused a dose-and time-dependent increase in Kfc values (8-15 fold), but the Tc-DTPA clearance rate was entirely unaffected. Moreover, transbronchial application of C 2 toxin again reproduced the manifold increase in Kfc data (about six fold), but the rate of transepithelial passage of the hydrophilic Tc-DTPA complex remained unchanged.We conclude that the barrier properties of the lung microvascular endothelial and epithelial layer are differentially regulated. It is suggested that the actin microfilament system plays a decisive role in the structural and functional integrity of the endothelial but not the epithelial barrier. Eur Respir J., 1996, 9, 93-99

Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation

“…Permeability to proteins of the epithelial and endothelial layers widely differs, alveolar epithelium being much less permeable than the endothelium (21). The alveolocapillary membrane may face physical, chemical, or biological insults, and the response of the epithelial or endothelial layers may differ depending on insult type (1,17,25,27,32,54). For example, Pseudomonas aeruginosa elastase on the alveolar side produces alveolar epithelium leakiness that manifests as an increase in the clearance of aerosolized albumin, without evidence of edema (1), whereas chronic heart failure due to large cardiac infarcts increases protein fluxes in both directions (11).…”

Real Time Lung Imaging for the Detection of Lung Injury and Alveolar Fluid Movement During Mechanical Ventilation

“…Relationship between changes in the alveolar concentration of the tracer (C/C 0 ) and the permeability surface area product of the alveolar epithelium: as previously published [37], the rate of solute diffusion (dQ/dt) through membranes is directly proportional to membrane surface area (S) and the concentration gradient (dc/dx) in accordance with Fick's First Law of Diffusion: dQ/dt = -DS dc/dx (2) where D represents the diffusion coefficient per unit of surface area. As the concentration difference across the membrane c can only be measured, this equation becomes:…”

“…Moreover, the response of each layer of the alveolo-capillary membrane to physical, chemical or biological insults may differ, depending on insult type [2,4,5]. For instance, Pseudomonas aeruginosa elastase on the alveolar side produces alveolar epithelium leakiness that manifests as an increase in the clearance of aerosolized albumin, without evidence of edema [1], whereas chronic heart failure increases protein fluxes in both directions [56].…”

“…The alveolocapillary barrier is thin enough to allow efficient gas exchange and strong enough to prevent the burst of plasma proteins and water into alveoli. This barrier may however experience physical, chemical or biological insults that lead to an increased permeability to proteins [1][2][3][4][5]. Because the permeability of the alveolo-capillary membrane to water is much greater than that to proteins, the measurement of extravascular lung water is rather insensitive for detecting pulmonary edema of the permeability type.…”

Upregulation of immunoreactivity of endothelin‐1 and α‐SMA in PDL microvasculature following acute tooth loading: an immunohistochemical study in the marmoset

“…The actin cytoskeleton is thought to play a decisive role in modulating cellular morphology and function (12), and in maintaining the structural and functional integrity of the endothelial barrier (20). Liu and Sundqvist (16) think that the peripheral actin system is responsible for alterations in endothelial permeability.…”