title: Airway eosinophil migration into lymph nodes in mice depends on leukotriene C4.
abstract: BACKGROUND
  We previously demonstrated in mice that airway eosinophils traffic from the airway lumen into lung-draining paratracheal lymph nodes. However, mechanisms whereby eosinophils traverse from the lungs and home to paratracheal lymph nodes remain unclear. We investigated roles of cysteinyl leukotrienes in mediating eosinophil trafficking from lungs to paratracheal lymph nodes.
  
  
  METHODS
  The expression of CCR7 was determined by flow cytometry. Transwell assays were used to test chemotactic responses of leukotriene C4synthase-deficient and control airway eosinophils to the chemokine CCL19 ex vivo. Eosinophils from the spleens of IL-5 transgenic mice, fluorescently labeled ex vivo, were intratracheally injected into ovalbumin-sensitized and ovalbumin aerosol-challenged leukotriene C4synthase-deficient and control mice. Eosinophils were identified by microscopy and flow cytometry in the lungs and paratracheal lymph nodes.
  
  
  RESULTS
  Mouse eosinophils expressed CCR7, the receptor for CCL19, and responded chemotactically to CCL19. Leukotriene C4synthase-deficient eosinophils exhibited impaired chemotaxis to CCL19 that was restored by exogenous leukotriene C4. The migration of intratracheally injected eosinophils into paratracheal lymph nodes from distal alveolar lung was diminished in leukotriene C4synthase-deficient mice compared with wild-type mice, with increased retention of eosinophils in the lungs of leukotriene C4synthase-deficient mice. Exogenous administration of leukotriene C4restored trafficking of eosinophils to paratracheal lymph nodes in leukotriene C4synthase-deficient mice.
  
  
  CONCLUSIONS
  Our findings that cysteinyl leukotrienes are involved in regulating airway and lung eosinophil migration into paratracheal lymph nodes identify previously unrecognized roles for the cysteinyl leukotrienes in regulating the pulmonary trafficking of eosinophils in experimental allergic asthma.
authors.affiliation: Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: H-B
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of California San Diego, San Diego, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Akuthota
authors.affiliation: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Kanaoka
authors.affiliation: Division of Allergy and Inflammation, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Weller
mesh_terms: D000818:Animals; D001249:Asthma / Q000473:pathology; D054415:Chemokine CCL19 / Q000502:physiology; D002633:Chemotaxis; D004804:Eosinophils / Q000166:cytology* / Q000378:metabolism; D017997:Leukotriene C4 / Q000008:administration & dosage / Q000172:deficiency / Q000276:immunology*; D008168:Lung / Q000166:cytology; D008198:Lymph Nodes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D054400:Receptors, CCR7 / Q000502:physiology
chemical_list: C515461:Ccl19 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D054400:Receptors, CCR7; D017997:Leukotriene C4
keywords: CCR7 receptor; asthma; cysteinyl leukotrienes; eosinophils; lymph node trafficking