Release of Endotoxin-binding Proteins during Major Elective Surgery: Role of Soluble CD14 in Phagocytic Activation

Abstract.

Our previous study demonstrated that soluble CD14 (sCD14) modulates the biologic activity of circulating endotoxin, which appears after surgery. In this study, we examined the behavior of endotoxin-binding proteins, such as sCD14, lipopolysaccharide-binding protein (LBP), and bactericidal/permeability-increasing protein (BPI), in patients' plasma after major abdominal surgery and the phagocytic secretion of sCD14 from peripheral blood mononuclear cells (PBMCs) throughout the observation period. In a prospective study, 15 patients undergoing major abdominal surgery (gastrectomy, n= 3; pancreatectomy, n= 10; colectomy, n= 2) were involved in this study. The endotoxin-binding proteins were perioperatively (preoperatively; postoperative hour 6; days 1, 2, 3, 4, 5, 7, and 10) measured by an enzyme-linked immunosorbent assay (ELISA). To exclude the hemodilution effect of samples, each parameter was corrected by dividing the respective value by the albumin concentration. The phagocytic activity at each time point was tested as an ex vivo sCD14 secretion from PBMCs in the presence and absence of exogenously added endotoxin, Escherichia coli 055B5 (1 ng/ml). Significant endotoxemia (0.35 ± 0.13 EU/ml; p < 0.05) was observed 6 hours after the beginning of surgery. The sCD14/albumin value rapidly increased at 6 hours after surgery, peaked on day 1, and sequentially declined, whereas the BPI/albumin and LBP/albumin ratios increased more gradually and peaked on day 2. The secretion of sCD14 from 2 × 10⁶ PBMCs was significantly enhanced from 6 hours after operation. The increased plasma level of sCD14 may be explained by the parallel-enhanced sCD14 PBMC production. Activated secretion of these endotoxin-binding proteins may play a role in regulating the biologic activity of circulating endotoxin.