Actin-containing sera from patients with adult respiratory distress syndrome are toxic to sheep pulmonary endothelial cells

Actin released from damaged cells after a variety of tissue injuries appears to be involved in multiple organ dysfunction syndrome. Under experimental conditions, when the quantity of actin present in plasma is made to exceed the protective capacity of the actin-scavenging mechanism, microembolism a...

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Published in:	American journal of respiratory and critical care medicine Vol. 162; no. 1; pp. 288 - 294
Main Authors:	ERUKHIMOV, J. A, TANG, Z.-L, JOHNSON, B. A, DONAHOE, M. P, RAZZACK, J. A, GIBSON, K. F, LEE, W. M, WASSERLOOS, K. J, WATKINS, S. A, PITT, B. R
Format:	Journal Article
Language:	English
Published:	New York, NY American Lung Association 01-07-2000
Subjects:	Actins - blood Actins - toxicity Animals Bacterial diseases Bacterial diseases of the respiratory system Biological and medical sciences Cells, Cultured Endothelium, Vascular - cytology Human bacterial diseases Humans Infectious diseases Medical sciences Pulmonary Artery - cytology Respiratory Distress Syndrome, Adult - blood Sheep Cell culture Endothelial cell Pneumonia Binding protein Actin Blood vessel Complication Serum Biological effect Gelsolin Ungulata Human Lung disease Exogenous Pathophysiology Respiratory disease Pulmonary artery Infection Vertebrata Mammalia Adult respiratory distress syndrome Animal Bacteriosis Sheep Artiodactyla
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Summary:	Actin released from damaged cells after a variety of tissue injuries appears to be involved in multiple organ dysfunction syndrome. Under experimental conditions, when the quantity of actin present in plasma is made to exceed the protective capacity of the actin-scavenging mechanism, microembolism and pulmonary vascular angiopathy have been noted in rats. It remains to be determined whether this injury is a result of a direct toxic effect or occurs indirectly via platelet activation or fibrin interactions. We examined the effect of sera from patients with adult respiratory distress syndrome (ARDS), as well as G-actin added to normal serum, on the viability, morphology, and function of cultured sheep pulmonary artery endothelial cells (SPAEC). Both patient sera and normal sera to which actin was added were toxic in the cell culture model; this toxicity could be abrogated, at least partially, by preincubation with gelsolin, which is known to complex with actin. A significant portion of the toxicity of sera from patients with ARDS was sensitive to heat (56 degrees C), suggesting an important role of complement. Sera from patients with ARDS were shown to contain filaments of F-actin by immunoblot and rhodamine phalloidin staining after ultracentrifugation. Thus, saturation of the actin-scavenging system by addition of exogenous G-actin to plasma produces direct pulmonary endothelial cell injury. Furthermore, plasma from patients with ARDS secondary to bacterial pneumonia is toxic to SPAEC, and a small but significant contributory role of actin is apparent in these studies.
ISSN:	1073-449X 1535-4970
DOI:	10.1164/ajrccm.162.1.9806088