Alterations in plasma levels and complexing of Gc (vitamin D-binding protein) in rats with endotoxic shock

Septic shock is known to involve increased metabolism of arachidonic acid and generation of certain eicosanoids. Recently, a new extracellular pool of unsaturated fatty acids including arachidonate has been found in relation to group-specific component (Gc), a vitamin D-binding plasma protein that sequesters monomeric G-actin. Since complexing with G-actin displaces fatty acids, possible alterations in plasma levels of Gc and extent of complexing were sought in serial samples obtained from rats with shock induced by Salmonella enteritidis endotoxin (12.5-15 mg kg-1). Gc levels in animals receiving endotoxin exhibited bimodal alterations, with a significant reduction (P less than 0.001) at 1 hour, followed by a progressive elevation to 160% of starting concentrations at 6 days in animals that survived, whereas in sham-injected animals the change observed was a continuous rise to 147% at 6 days. A statistically significant increase in the percentage of Gc complexed was observed in all endotoxemic rats from 2 hours onward (P less than 0.01), in contrast to sham-injected animals, in which the percentage of Gc complexed remained at less than 5%. Levels in survivors peaked at 30 +/- 5.2% at 8 hours and then decreased to normal (2 +/- 0.9%) by 6 days (n = 7), whereas in nonsurvivors complexed Gc continued to rise until time of death (66-80%) at 6-12 hours (n = 4). Correlation of these results with glucose, transaminases, and immunoreactive TXB2 and 6-keto-PGF1 alpha indicated that decreased absolute levels of Gc represent a consistent early change in endotoxic shock and that the percentage of Gc complexed is an accurate prognostic indicator of severity.