Abstract
BackgroundDepletion of the circulating actin-binding protein, plasma gelsolin (pGSN) has been described in septic patients and animals. We hypothesized that the extent of pGSN reduction correlates with outcomes of septic patients and that circulating actin is a manifestation of sepsis.Methodology/Principal FindingsWe assayed pGSN in plasma samples from non-surgical septic patients identified from a pre-existing database which prospectively enrolled patients admitted to adult intensive care units at an academic hospital. We identified 21 non-surgical septic patients for the study. Actinemia was detected in 17 of the 21 patients, suggesting actin released into circulation from injured tissues is a manifestation of sepsis. Furthermore, we documented the depletion of pGSN in human clinical sepsis, and that the survivors had significantly higher pGSN levels than the non-survivors (163±47 mg/L vs. 89±48 mg/L, p = 0.01). pGSN levels were more strongly predictive of 28-day mortality than APACHE III scores. For every quartile reduction in pGSN, the odds of death increased 3.4-fold.ConclusionWe conclude that circulating actin and pGSN deficiency are associated with early sepsis. The degree of pGSN deficiency correlates with sepsis mortality. Reversing pGSN deficiency may be an effective treatment for sepsis.
Highlights
Plasma gelsolin is the secreted isoform of cytoplasmic gelsolin, an intracellular actin-binding protein that regulates cell motility [1]. plasma gelsolin (pGSN) circulates in normal plasma at 190–300 mg/L [2]
We conclude that circulating actin and pGSN deficiency are associated with early sepsis
Tissue injury has not been clearly documented in early sepsis, low pGSN levels have been reported in sepsis patients [6], and a recent paper reported reduced pGSN levels in surgical sepsis patients [11]
Summary
Plasma gelsolin (pGSN) is the secreted isoform of cytoplasmic gelsolin (cGSN), an intracellular actin-binding protein that regulates cell motility [1]. pGSN circulates in normal plasma at 190–300 mg/L [2]. Plasma gelsolin (pGSN) is the secreted isoform of cytoplasmic gelsolin (cGSN), an intracellular actin-binding protein that regulates cell motility [1]. Similar to cGSN, pGSN binds actin, a major body protein that may be exposed or released by cellular injury. Further studies have revealed that critical extents of pGSN depletion in patients subjected to trauma, burns, major surgery or hematopoietic stem cell transplantation correlate with poor outcomes, including death [7,8,9]. Circulating actin is detectable in the septic animals, and pGSN replacement converts it from an aggregated to a more soluble state [12]. We undertook a pilot study to determine whether actin appears in the circulation of septic humans and if pGSN decreases correlate with outcomes in nonsurgical sepsis patients
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