The Duffy antigen receptor for chemokines (DARC) ‐ A link between inflammation and hemostasis?

Abstract

Chemokines and their receptors play a pivotal role in PMN recruitment during inflammation and in platelet activation. DARC differs from 'typical’ chemokine receptors in that it is not known to initiate intracellular signal transduction and that it is expressed on red blood cells and endothelial cells rather than on leukocytes. Here, we first studied the role of DARC in a murine, neutrophil (PMN)-dependent model of HCl-induced acute lung injury (ALI). Wild-type mice (WT) experienced severe hypoxemia 2h after intratracheal HCl-instillation (sham paO2 134±13mmHg, ALI paO2 47±5 mmHg, p<0.05) and a more than two-fold increase in lung myeloperoxidase activities (MPO, p<0.05), indicating strong pulmonary PMN recruitment. By contrast, DARC gene-deficient mice (DARC−/−) demonstrated no significant changes in paO2 and in lung MPO. When compared to WT, DARC−/− also exhibited a significanltly prolonged bleeding time (WT median 57sec, DARC−/− median 107sec, p<0.05) despite normal and statistically not different platelet counts (WT 702954±26073/μl, DARC−/− 638068±28771/μl). In conclusion, we show that DARC can act as a modulator of inflammatory PMN recruitment and subsequent lung injury and as a key factor in platelet-dependent pathways of hemostasis. Thus, DARC might represent a new link between inflammation and hemostasis. (This work was supported by a research grant from the Else Kröner-Fresenius-Stiftung to KS.)