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Duffy antigen modifies the chemokine response in human endotoxemia

Mayr, Florian B. MD; Spiel, Alexander O. MD; Leitner, Judith M. MD; Firbas, Christa MD; Kliegel, Tuende MSc; Jilma-Stohlawetz, Petra MD; Derendorf, Hartmut PhD; Jilma, Bernd MD

doi: 10.1097/01.CCM.0000297875.55969.DB
Clinical Investigations

Objective: 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.

Design: Prospective, analyst-blinded clinical trial.

Patients: A total of 32 healthy male volunteers: 16 Duffy-positive white subjects and 16 Duffy-negative subjects of African descent.

Measurements and Main Results: 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.

Results: Plasma levels of tumor necrosis factor, interleukin-6, interleukin-10, and whole blood growth-related oncogen-α, 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-α 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-α, and interleukin-8 increased 20- to 50-fold in Duffy-positive subjects (p < .00001 vs. baseline).

Conclusion: The Duffy antigen substantially alters chemokine concentrations in blood, but it does not have a protective effect during human endotoxemia.

From the Departments of Clinical Pharmacology (FBM, AOS, JML, CF, TK, BJ) and Blood Group Serology and Transfusion Medicine (PJS), Medical University of Vienna, Austria; Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL (PJS, HD, BJ); and the CRISMA Laboratory, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA (FBM).

The authors have not disclosed any potential conflicts of interest.

Supported, in part, by grant T32 HL007820-10 from the National Institutes of Health, Bethesda, MD (Dr. Mayr), and by an Erwin Schroedinger Stipendium (J2409) from the Austrian Science Funds, Vienna, Austria (Dr. Jilma).

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© 2008 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins