Overexpression of the High-affinity Fcgamma Receptor (CD64) is Associated with Leukocyte Dysfunction in Sepsis

The morbidity and mortality from sepsis and multiple organ dysfunction syndrome (MODS) continues to be high. An increase in FcgammaRI+ (CD64+) monocytes was demonstrated in septic patients, and an association between cell number, their secretory activity, and poor outcome has been described. In the present investigation further characterization of CD64+ leukocytes has been attempted. The study was aimed at examining the phagocytic activity (PA) and reactive oxygen species (ROS) production by monocytes (Mo) and neutrophils (Neu) in sepsis and sepsis-induced acute respiratory distress syndrome (ARDS) related to the pattern of CD64 expression. Twenty-three post-traumatic or post-operative male and female patients with sepsis were enrolled. The control group consisted of 10 healthy volunteers. Arterial blood samples were taken during the septic episode for flow cytometric analysis of surface leukocyte antigens, phagocytosis, and ROS production. CD64 expression on Mo and Neu was markedly increased in septic patients (P = 0.029 and P = 0.0005), and even more in sepsis with ARDS (P = 0.011). In healthy individuals, PA of CD64+ Neu was higher, than of CD64- cells (P = 0.021). In septic patients, decreased PA was detected in CD64+ Mo and Neu (P = 0.013 and P = 0.040, respectively). CD64+ Neu of patients in ARDS exhibited the most prominent PA depression (P = 0.048). ROS production in non-separated Mo and Neu was increased in sepsis (P = 0.026 and P = 0.004, respectively). In healthy individuals CD64+ Neu and stimulated CD64+ Mo demonstrated increased ROS synthesis compared to matched CD64- cells (P = 0.001 and P = 0.042, respectively). Although ROS production by CD64+ leukocytes in sepsis was also increased compared to CD64- cells, significantly less ROS was generated compared to healthy subjects (P = 0.021). In conclusion, overexpression of CD64 on blood Mo and Neu from patients with sepsis and ARDS is associated with depressed PA and decreased oxidative response.