Submitted November 13, 2006
Accepted May 23, 2007
Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo
Rahima Zennadi, Benjamin J Moeller, Erin J Whalen, Milena Batchvarova, Ke Xu, Siqing Shan, Martha Delahunty, Mark W Dewhirst, and Marilyn J. Telen*
Division of Hematology, & Duke Comprehensive Sickle Cell Center, Duke University Medical Center, Durham, NC, United States
Department of Radiation Oncology, Duke University Medical Center, Durham, NC, United States
Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC, United States
* Corresponding author; email: telen002{at}mc.duke.edu.
Sickle red cell (SS RBC) adhesion is believed to contribute to the process of vaso-occlusion in sickle cell disease (SCD). We previously found that the LW RBC adhesion receptor can be activated by epinephrine to mediate SS RBC adhesion to endothelial
v
3 integrin. To determine the contribution of LW activation to vaso-occlusive events in vivo, we investigated whether in vitro treatment of SS RBCs by epinephrine resulted in vaso-occlusion in intact microvasculature after RBC infusion into nude mice. Epinephrine enhanced human SS but not normal RBC adhesion to murine endothelial cells in vitro and to endothelium in vivo, promoting vaso-occlusion and RBC organ sequestration. Murine sickle RBCs also responded to epinephrine with increased adhesion to postcapillary endothelium in nude mice. Epinephrine-induced SS RBC adhesion, vaso-occlusion and RBC organ trapping could be prevented by the
-adrenergic receptor (AR) antagonist, propranolol. Infusion of soluble recombinant LW also significantly reduced adhesion and vaso-occlusion. In addition, epinephrine-treated SS RBCs induced activation of murine leukocyte adhesion to endothelium as well. We conclude that LW activation by epinephrine via
-AR stimulation can promote both SS RBC and leukocyte adhesion as well as vaso-occlusion, suggesting that both epinephrine and LW play potentially pathophysiological roles in SCD.