Haemopoietic mechanisms in murine allergic upper and lower airway inflammation.
Eosinophil recruitment to the airways, including involvement of haemopoietic eosinophil-basophil progenitors (Eo/B-CFU), is primarily regulated by interleukin-5 (IL-5) and eotaxin. In this study, we investigated the haemopoietic mechanisms in upper and lower airway eosinophilic inflammation. Ovalbumin (OVA) sensitized and challenged BALB/c mice were used to establish isolated upper (UAC), isolated lower (LAC), or combined upper and lower airway (ULAC) inflammation. Airway, blood and bone marrow responses were evaluated in each model. Numbers of airway eosinophils and CD4(+) cells were increased significantly in the nasal mucosa in UAC and ULAC mice, and in the lung tissue in LAC and ULAC groups. Levels of IL-5 and eotaxin were increased significantly in the nasal lavage fluid (NL) in UAC and ULAC mice, and in the bronchoalveolar lavage fluid (BAL) in LAC and ULAC groups. The proportion of IL-5-responsive bone marrow Eo/B-CFU was significantly higher than the control in all treatment groups, but peaked much earlier in the ULAC group. Kinetic studies revealed that IL-5 and eotaxin in NL, BAL and serum peaked between 2 and 12 hr after OVA challenge in ULAC mice, and at 24 hr in UAC mice, related to the timing of maximal progenitor responses. These data support the concept that the systemic mechanisms linking rhinitis to asthma depend on the location and extent of airway allergen exposure.
Li
Jing
J
Department of Medicine, Division of Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario, Canada.
Saito
Hiroko
H
Crawford
Lynn
L
Inman
Mark D
MD
Cyr
Michael M
MM
Denburg
Judah A
JA
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000032:analysis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology; D005260:Female; D006410:Hematopoiesis / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D018928:Immunity, Mucosal; D015848:Interleukin-5 / Q000032:analysis; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D017817:Nasal Lavage Fluid / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D012220:Rhinitis / Q000276:immunology* / Q000473:pathology
D018952:Antigens, CD34; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D015848:Interleukin-5; D010047:Ovalbumin
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