Expression of Human CXCR2 in Murine Neutrophils as a Model for Assessing Cytomegalovirus Chemokine vCXCL-1 Function In Vivo

Abstract

Human cytomegalovirus (CMV) (Toledo strain) produces a potent chemokine (vCXCL-1) that specifically recognizes human (Hu)CXCR2, one of two human CXCL8 (IL8) receptors found on peripheral blood neutrophils. Thioglycollate-elicited neutrophils from BALB/c mice failed to respond to vCXCL-1 while retaining the capacity to respond to known murine (Mu) CXCR2 ligands, such as hCXCL8 (IL8) and mCXCL1 (KC). A transgenic mouse expressing hCXCR2 under the control of a neutrophil-specific promoter (human myeloidrelated protein-8) was generated. Resting or activated neutrophils from transgenic mice were found to express hCXCR2 and to respond to vCXCL-1. vCXCL-1 induced a specific calcium flux and chemotaxis of these cells. Expression of the functional vCXCL-1 receptor in mice will facilitate investigations of the role vCXCL- 1 plays during viral infection of an intact host animal. In addition, this work demonstrates the remarkable species specificity of a potent viral chemokine.