Depression of gelsolin levels and detection of gelsolin-actin complexes in plasma of patients with acute lung injury

Abstract

Actin is the major protein of muscle and nonmuscle cells and is one of the most abundant body proteins. Physiologic or pathologic cell death may therefore result in the liberation of large amounts of this fibrous protein into the extravascular space. The potential for long actin filaments to increase plasma viscosity and change the rheology of the microvasculature are potentially obviated by the presence of 2 recently recognized plasma actin-binding proteins, vitamin-D-binding protein, and plasma gelsolin. As part of our initial evaluation of this newly recognized physiologic system in humans, we measured levels of gelsolin in plasma samples from patients with extensive lung injury. Gelsolin levels were depressed in 25 of 25 patients with the adult respiratory distress syndrome (ARDS), a disease characterized by massive cellular injury, as determined by either of 2 functional assays for gelsolin. Mean total gelsolin concentration of 20 patients with ARDS was 89.2 +/- 33 micrograms/ml (normal levels, approximately 240 micrograms/ml; p less than 0.001) and the mean free gelsolin concentration 69.6 +/- 29 micrograms/ml (normal levels, approximately 240 micrograms/ml; p less than 0.001). Gelsolin concentrations of 6 patients with bacterial pneumonias were also depressed, but to a lesser degree (mean total level, 117 +/- 21 micrograms/ml). Direct demonstration of the presence of actin in these plasmas (but not in normal plasmas) was performed by precipitating actin directly with DNase-Sepharose beads, or indirectly with antigelsolin-Sepharose beads, as confirmed with immunoblotting. Actin was found in 18 of 19 patients using DNase beads and in 7 of 19 using antigelsolin beads.(ABSTRACT TRUNCATED AT 250 WORDS)