title: Activation of basophils by the double-stranded RNA poly(A:U) exacerbates allergic inflammation.
abstract: BACKGROUND
  It is commonly acknowledged that asthma is exacerbated by viral infections. On the other hand, basophil infiltration of lung tissues has been evidenced postmortem in cases of fatal disease, raising the question of a possible link between these two observations.
  
  
  OBJECTIVE
  Herein, we addressed the relationship between asthma exacerbation by viral infection and basophil activation and expansion by investigating how stimulation with the dsRNA polyadenylic/polyuridylic acid [poly(A:U)] affected basophil activities and recruitment in an allergic airway inflammation model.
  
  
  METHODS
  The effect of dsRNA on basophils was assessed by measuring the cytokine levels produced upon stimulation. We used an OVA-induced experimental model of allergic asthma. Airway hyperreactivity, recruitment of infiltrating cells, and cytokine production were determined in the lung of mice having received poly(A:U), as compared with untreated controls. The exacerbating effect of basophils was assessed both by adoptive transfer of poly(A:U)-treated basophils and by their in vivo depletion with Ba103 antibody.
  
  
  RESULTS
  We found that in vitro treatment with poly(A:U) increased basophil functions by inducing TH 2-type cytokine and histamine production, whereas in vivo treatment increased peripheral basophil recruitment. Furthermore, we provide the first demonstration for increased infiltration of basophils in the lung of mice suffering from airway inflammation. In this model, disease symptoms were clearly exacerbated upon adoptive transfer of basophils exposed to poly(A:U), relative to their unstimulated counterpart. Conversely, in vivo basophil depletion alleviated disease syndromes, thus validating the transfer data.
  
  
  CONCLUSIONS
  Our findings provide the first evidence for airway inflammation exacerbation by basophils following dsRNA stimulation.
authors.affiliation: Faculty of Medicine, Necker Hospital, Paris Descartes University, Paris, France; CNRS UMR 8147, Necker Hospital, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Ramadan
authors.forename: L
authors.initials: L
authors.lastname: Pham Van
authors.forename: F
authors.initials: F
authors.lastname: Machavoine
authors.forename: C
authors.initials: C
authors.lastname: Dietrich
authors.forename: M
authors.initials: M
authors.lastname: Alkan
authors.forename: H
authors.initials: H
authors.lastname: Karasuyama
authors.forename: E
authors.initials: E
authors.lastname: Schneider
authors.forename: M
authors.initials: M
authors.lastname: Dy
authors.forename: N
authors.initials: N
authors.lastname: Thieblemont
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000821:virology; D001491:Basophils / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006632:Histamine / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D011063:Poly A-U / Q000008:administration & dosage / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D012330:RNA, Double-Stranded; D011063:Poly A-U; D006632:Histamine