Recombinant plasma gelsolin infusion attenuates burn-induced pulmonary microvascular dysfunction

Patricia A. Rothenbach, Benny Dahl, Jason J. Schwartz, Grant E. O'Keefe, Masaya Yamamoto, William M. Lee, Jureta W. Horton, Helen L. Yin, Richard H. Turnage

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Reduced plasma concentrations of the extracellular actin-binding proteins gelsolin and Gc-globulin correlate with pulmonary failure and death in humans after injury. The purpose of this study was to investigate the role of plasma gelsolin in the pathophysiology of inflammation-induced lung injury. We postulated that plasma gelsolin levels decrease at an early time point after burn injury and that the intravenous infusion of gelsolin prevents burn-induced pulmonary microvascular dysfunction. Adult Sprague-Dawley rats were randomized to undergo a 40% body surface area thermal injury (Burn) or manipulation without burn (Sham). Plasma gelsolin and Gc-globulin concentrations were determined at various times during the first 6 days of injury by Western blotting. Other animals were randomized to receive either recombinant human gelsolin (0.078, 0.78, or 7.8 mg) or albumin (7.8 mg) before and 8 h after Burn or Sham. Twenty-four hours later, pulmonary microvascular permeability was assessed by measuring the capillary filtration by use of an isolated, perfused lung model. We found that plasma gelsolin levels of burn-injured rats decreased to 10% of normal levels within 12 h and remained below normal levels for up to 6 days postinjury. Gc-globulin values also fall, but to a lesser extent and only transiently. Treatment of burned animals with intravenous infusions of recombinant human gelsolin prevented the increase in pulmonary microvascular permeability that accompanies this injury. Our findings are consistent with the hypothesis that plasma gelsolin depletion contributes to the pathophysiology of pulmonary microvascular dysfunction during inflammation.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalJournal of applied physiology
Volume96
Issue number1
DOIs
StatePublished - Jan 2004

Keywords

  • Capillary filtration coefficient
  • Gc-globulin
  • Isolated perfused lung model
  • Microvascular permeability

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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