Airway epithelial cell-induced activation of monocytes and eosinophils in respiratory syncytial viral infection.
The early inflammatory events in respiratory syncytial viral (RSV) infection are likely to be crucial in the development of clinical disease, which is characterized by bronchiolitis with mononuclear cell inflammation, some eosinophil involvement and airway hyperreactivity. Since RSV replication is restricted to airway epithelial cells, our working hypothesis is that inflammatory cell recruitment by the infected cells will set the stage for late immunopathology. We have identified the selective induction and release of mononuclear cell and eosinophil-attracting beta-chemokines MIP-1alpha and RANTES, but not eotaxin, by RSV-infected airway epithelial cells and herein demonstrated the recruitment of eosinophils and monocytes, but not neutrophils, in response to chemokines produced by infected epithelial cells during viral replication and dissemination. The chemotactic response of both eosinophils and monocytes was inhibited by antibodies to RANTES but not to MIP-1alpha. Interaction of eosinophils or monocytes with RSV-infected epithelial cells resulted in the production of additional beta-chemokines MCP-1 and MIP-1beta, and increased levels of MIP-1alpha. The monocyte containing cultures produced >10 fold the amount of these chemokines compared to eosinophil containing cultures. On the other hand, the levels of RANTES and the lack of eotaxin were not altered in the cocultures, RSV-infected monocytes appeared to be the main source of MIP-1alpha and MIP-1beta, while MCP-1 was derived from monocytes as well as epithelial cells following coculture. These data implicate RANTES as the primary chemokine responsible for selectively recruiting eosinophils and monocytes to the site of RSV infection. This inflammatory response results in the production of high levels of additional chemokines capable of setting up a full-fledged inflammatory response including lymphocytes.
Becker
S
S
US EPA, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC, USA. becker.susanne@epamail.epa.gov
Soukup
J M
JM
D002460:Cell Line; D019742:Chemokines, CC / Q000096:biosynthesis; D004804:Eosinophils / Q000276:immunology* / Q000821:virology; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D005260:Female; D006801:Humans; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000821:virology; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology* / Q000502:physiology; D014407:Tumor Cells, Cultured
D019742:Chemokines, CC