title: Endothelial damage from cytomegalovirus-specific host immune response can be prevented by targeted disruption of fractalkine-CX3CR1 interaction.
abstract: Human cytomegalovirus (CMV) infection has been linked to inflammatory diseases, including vascular disease and chronic transplant rejection, that involve vascular endothelial damage. We have previously shown that the host CD4(+) T-cell response to CMV antigen can produce IFNgamma and TNFalpha at levels sufficient to drive induction of fractalkine, a key marker of inflammation in endothelial cells. We have also observed a major pathogenic effect in which endothelial cell damage and loss follow the induction of fractalkine and up-regulation of cell adhesion markers in the presence of peripheral blood mononuclear cells (PBMCs) from donors with a high CMV-specific T-cell frequency. In this report, we show that the fractalkine-CX(3)CR1 interaction resulting in recruitment of natural killer (NK) cells and monocyte-macrophages plays an important role in mediating this endothelial damage. Supportive evidence for frac-talkine's key role is shown by the ability of specific antibody to CX(3)CR1 to reduce significantly CX(3)CR1(+)-bearing cell chemoattraction and to protect against endothelial damage. These findings support CMV as a member of a class of persistent pathogens in which a high T-cell response and chemokine-mediated effects are a risk factor for development of chronic inflammation and endothelial cell injury.
authors: Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, CA 92093-0672, USA.
authors: Cynthia A
authors: CA
authors: Bolovan-Fritts
authors: Stephen A
authors: SA
authors: Spector
mesh_terms: D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology / Q000494:pharmacology; D000956:Antigens, Viral / Q000276:immunology / Q000494:pharmacology; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D018920:Coculture Techniques; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D019707:Receptors, Chemokine / Q000378:metabolism*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D018950:Lipopolysaccharide Receptors; D019707:Receptors, Chemokine