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

Jeffrey A. Erukhimov, Zi Lue Tang, Bruce A. Johnson, Michael P. Donahoe, Jamal A. Razzack, Kevin F. Gibson, William M. Lee, Karla J. Wasserloos, Simon A. Watkins, Bruce R. Pitt

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

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°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.

Original languageEnglish (US)
Pages (from-to)288-294
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume162
Issue number1
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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