title: Respiratory syncytial virus-induced CCL5/RANTES contributes to exacerbation of allergic airway inflammation.
abstract: Severe respiratory syncytial virus (RSV) infection has a significant impact on airway function and may induce or exacerbate the response to a subsequent allergic challenge. In a murine model combining early RSV infection with later cockroach allergen (CRA) challenge, we examined the role of RSV-induced CCL5/RANTES production on allergic airway responses. RSV infection increased CCL5 mRNA and protein levels, peaking at days 8 and 12, respectively. Administration of CCL5 antiserum during days 0-14 of the RSV infection did not significantly alter viral protein expression when compared to mice treated with control serum. In mice receiving the combined RSV-allergen challenge, lungs collected on day 22 exhibited significantly increased numbers of CD4- and CD8-positive T cells. This increase in T cell numbers was not observed in mice receiving alpha-CCL5. On day 43, peribronchial eosinophilia and leukotriene levels were increased in RSV-allergen mice. Pretreatment with CCL5 antiserum resulted in decreased recruitment of inflammatory cells to bronchoalveolar and peribronchial regions of the lungs and these reductions were associated with a reduction in both T cell recruitment into the bronchoalveolar space, leukotriene release and chemokine generation. Thus, CCL5 released during RSV infection has a significant effect on the inflammatory response to subsequent allergic airway challenges.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, USA.
authors.forename: Alison E
authors.initials: AE
authors.lastname: John
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Berlin
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000209:etiology; D001980:Bronchi / Q000276:immunology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D018925:Chemokines / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte; D003058:Cockroaches / Q000276:immunology; D004802:Eosinophilia / Q000209:etiology; D005260:Female; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral; D006801:Humans; D007106:Immune Sera; D007249:Inflammation; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D023421:Models, Animal; D012130:Respiratory Hypersensitivity / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D013047:Specific Pathogen-Free Organisms; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: D000485:Allergens; D018946:Chemokine CCL5; D018925:Chemokines; D007106:Immune Sera; D015289:Leukotrienes; D014764:Viral Proteins