Duffy antigen modifies the chemokine response in human endotoxemia

Abstract

The Duffy receptor is a promiscuous receptor for chemokines and selectively binds CXC and CC chemokines with high affinity. Preclinical data show that presence of the Duffy receptor on red blood cells may influence plasma levels of proinflammatory cytokines and chemokines and be protective during inflammation. This trial was designed to investigate the influence of the Duffy antigen on human inflammation in vivo. Prospective, analyst-blinded clinical trial. A total of 32 healthy male volunteers: 16 Duffy-positive white subjects and 16 Duffy-negative subjects of African descent. All subjects received an intravenous bolus of 2 ng/kg endotoxin (lipopolysaccharide). Cytokines, chemokines, and their receptors were quantified by enzyme immunoassay, reverse transcriptase-polymerase chain reaction, and flow cytometry. Plasma levels of tumor necrosis factor, interleukin-6, interleukin-10, and whole blood growth-related oncogen-alpha, monocyte chemoattractant protein-1, and interleukin-8 messenger RNA increased similarly in both groups after lipopolysaccharide infusion. Monocyte chemoattractant protein-1 peak plasma levels were roughly two-fold higher in Duffy-positive subjects compared with Duffy-negative subjects (16 ng/mL vs. 7 ng/mL, p < .0001). Similarly, growth-related oncogen-alpha levels were 2.5-fold higher in Duffy-positive subjects 2 hrs after lipopolysaccharide infusion (210 pg/mL vs. 85 pg/mL; p < .001). Erythrocyte-bound monocyte chemoattractant protein-1, growth-related oncogen-alpha, and interleukin-8 increased 20- to 50-fold in Duffy-positive subjects (p < .00001 vs. baseline). The Duffy antigen substantially alters chemokine concentrations in blood, but it does not have a protective effect during human endotoxemia.