Cytomegalovirus-infected endothelial cells recruit neutrophils by the secretion of C-X-C chemokines and transmit virus by direct neutrophil-endothelial cell contact and during neutrophil transendothelial migration.
Infection of endothelial cells with an endothelial cell-tropic clinical isolate of cytomegalovirus (CMV), C1FE, induced enhanced production of the neutrophil chemoattractant C-X-C chemokines interleukin-8 and GROalpha. Infected endothelial cell supernatants induced neutrophil chemotaxis in a transendothelial migration assay. Neutrophils acquired the CMV structural protein pp65 following either coculture with infected endothelial cells or transmigration through infected endothelium. The lack of CMV p72 expression in the neutrophils indicated that viral replication had not occurred in these cells. Of importance, neutrophils acquired infectious CMV during transmigration across infected endothelium and were subsequently able to transmit infectious virus to fibroblasts. Thus, CMV-infected endothelial cells can recruit neutrophils by the secretion of C-X-C chemokines and can transmit the virus to them by direct cell-to-cell contact and during neutrophil transendothelial migration, suggesting that the neutrophil-endothelial cell interaction plays an important role in virus dissemination in vivo.
Grundy
J E
JE
Department of Clinical Immunology, Royal Free Hospital School of Medicine, London, United Kingdom.
Lawson
K M
KM
MacCormac
L P
LP
Fletcher
J M
JM
Yong
K L
KL
D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism*; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D006133:Growth Substances / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000096:biosynthesis; D009504:Neutrophils / Q000276:immunology* / Q000821:virology*; D010750:Phosphoproteins / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000378:metabolism
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D017077:Culture Media, Conditioned; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa