Serum Gc-globulin in the early course of multiple trauma

Objectives: In patients with multiple trauma, actin released from damaged cells may cause severe circulatory disturbance due to thrombi formation. The aim of this study was to evaluate serum concentrations of the actin scavenger, Gc-globulin, in relation to the severity of injury and outcome. Design: Prospective, longitudinal, observational study. Setting: Trauma center at a university hospital. Patients: Twelve patients with multiple trauma, consecutively included, according to defined criteria. Interventions: None. Measurements and Main Results: Serum Gc-globulin concentrations were measured at the time of admission and daily thereafter for 1 wk or until death. In all patients, the Gc-globulin concentration was significantly low (p < .0001), and the proportion of Gc-globulin bound to actin was already increased compared with normal values (p < .0001) by the time of hospital arrival. There was an inverse correlation between the mean concentration of serum Gc-globulin in the first week after trauma and the Injury Severity Score (r = -0.72, p<.05). Surviving patients had a significantly (p<.05) higher concentration of serum Gc-globulin in the first week after trauma compared with nonsurvivors. Conclusions: Serum concentrations of Gc-globulin were significantly low in trauma patients. The reduction took place within 60 mins after injury. Because the normal half-life of Gc-globulin is almost 48 hrs, our observations suggest a marked consumption of Gc-globulin immediately after the trauma. This finding could be the first clinical evidence that Gc-globulin plays a role in the systemic inflammatory response syndrome after trauma. This result is supported by the finding that lack of Gc-globulin was related to nonsurvival and the severity of the trauma. (Crit Care Med 1998; 26:285-289) Gc-globulin (vitamin D binding protein) is a plasma protein synthesized in the liver, and is the main protein involved in plasma transportation of vitamin D[1,2]. Together with gelsolin, synthesized in skeletal muscle, Gc-globulin also constitutes an important part of the extracellular actin scavenger system-a system responsible for the binding and clearing of extracellular actin [2]. Actin is the predominating protein in mammalian cells and plays an important role in maintaining cell structure and motility [3]. Actin and other intracellular proteins are released into the extracellular space as a consequence of cell death [4]. On release, actin will polymerize into its filamentous form, F-actin. Gelsolin, synthesized in skeletal muscle, binds to F-actin and depolymerizes it into monomeric G-actin [5]. G-actin, in turn, binds to Gc-globulin, and the G-actin-Gc-globulin complex is cleared primarily by the liver, but also by the lungs and in the spleen [6,7]. In conditions with massive cell death, the extracellular actin scavenger system may be exhausted, leading to the presence of F-actin in the circulation. In animal experiments, F-actin may cause microthrombi and endothelial injury with organ failure [8]. Several clinical situations are characterized by a reduced concentration of serum Gc-globulin. These situations include septic shock and hepatic necrosis [4]. Two studies [9,10] have shown that serum Gc-globulin in patients with acetaminophen poisoning can predict mortality and outcome. An association between reduced concentrations of serum Gc-globulin, multiple organ dysfunction syndrome (MODS), and survival has been found in patients with fulminant hepatic failure [11]. Late death after multiple trauma is predominately caused by MODS [12,13]. A number of reports [14-18] have described mediators that contribute to the development of MODS after severe trauma, but the pathophysiology behind this condition is far from understood. Therefore, it is relevant to describe other substances that contribute to the development of this condition. Since reduced concentrations of Gc-globulin may play a key role in the development of MODS in conditions such as sepsis and hepatic failure, it could be speculated that serum concentrations of Gc-globulin are affected in patients with multiple trauma, where large amounts of actin could be released into the bloodstream. The objectives of the present study in patients with multiple trauma were: a) to measure serum concentrations of Gc-globulin, as well as serum concentrations of the Gc-globulin-G-actin complex; and b) to compare these measurements with the severity of trauma and survival rate of these patients.