Expression of human CXCR2 in murine neutrophils as a model for assessing cytomegalovirus chemokine vCXCL-1 function in vivo.
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 myeloid-related 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.
Sparer
Tim E
TE
Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. tsparer@utk.edu
Gosling
Jennifa
J
Schall
Thomas J
TJ
Mocarski
Edward S
ES
D000818:Animals; D019743:Chemokines, CXC / Q000235:genetics / Q000502:physiology*; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology / Q000821:virology; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018448:Models, Immunological; D009504:Neutrophils / Q000276:immunology* / Q000821:virology; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology
D019743:Chemokines, CXC; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins