FUNCTIONAL ROLE OF DUFFY ANTIGEN IN ENDOTHELIAL CELLS

University Of Washington, Seattle WA

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Abstract

Chemokines are produced at sites of tissue injury, but it is not known how chemokines cross the endothelium and are made available to circulating neutrophils. The main hypothesis of this proposal is that Duffy Antigen/Receptor for Chemokines (DARC), a CXC and CC chemokine receptor with an unknown biological function in post-capillary venular endothelial cells, participates in chemokine transport at this interface of leukocyte trafficking. The central goal of this study is to define whether endothelial cell DARC facilitates or down-regulates neutrophil recruitment, particularly as it pertains to pathological inflammatory processes such as Acute Respiratory Distress Syndrome (ARDS). The research design involves an immortalized human endothelial cell line transfected with DARC cDNA. The specific aims address DARC's potential impact on neutrophil transendothelial migration, role in chemokine transport, and effect on endothelial cell activation, This study will provide new information into the mechanisms of chemokine- mediated lung inflammation, and may form the basis for novel strategies directed toward modifying its untoward effects.