title: Allergen stimulates bone marrow CD34(+) cells to release IL-5 in vitro; a mechanism involved in eosinophilic inflammation?
abstract: The specific mechanisms that alter bone marrow (BM) eosinophilopoiesis in allergen-induced inflammation are poorly understood. The aims of this study were to evaluate (a) whether the number of BM CD34(+) cells is altered due to allergen sensitization and exposure in vivo and (b) whether BM CD34(+) cells produce and release interleukin (IL)-5, IL-3 and granulocyte macrophage-colony stimulating factor (GM-CSF) after stimulation in vitro. A mouse model of ovalbumin (OVA)-induced airway inflammation was used. Bone marrow CD34(+) cells were cultured in vitro and the cytokine release was measured by enzyme-linked immunosorbent assay. The IL-5-production from CD34(+) cells was confirmed by immunocytochemistry. Airway allergen exposure increased the number of BM CD34(+) cells (P = 0.01). Bone marrow CD34(+) cells produced IL-5 when stimulated with the allergen OVA in vitro, but not IL-3 or GM-CSF. Nonspecific stimulus with calcium ionophore and phorbol-myristate-acetate of BM CD34(+) cells caused release of IL-5, IL-3 and GM-CSF. The induced release of IL-5 was increased in alum-injected vs naive mice (P = 0.02), but was not affected by allergen sensitization and exposure. The release of IL-3 and GM-CSF was increased after allergen sensitization and exposure (P < 0.02). In conclusion, allergen can stimulate BM CD34(+) cells to produce IL-5 protein. It is likely that the CD34(+) cells have autocrine functions and thereby regulate the early stages of BM eosinophilopoiesis induced by airway allergen exposure. Alum, a commonly used adjuvant, enhances the release of IL-5 and may thereby enhance eosinophilopoiesis.
authors.affiliation: Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Internal Medicine, Göteborg University, Sweden.
authors.forename: A-K
authors.initials: AK
authors.lastname: Johansson
authors.forename: M
authors.initials: M
authors.lastname: Sjöstrand
authors.forename: M
authors.initials: M
authors.lastname: Tomaki
authors.forename: A-M
authors.initials: AM
authors.lastname: Samulesson
authors.forename: J
authors.initials: J
authors.lastname: Lötvall
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D001980:Bronchi / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D007249:Inflammation; D007377:Interleukin-3 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal
chemical_list: D000485:Allergens; D018952:Antigens, CD34; D007377:Interleukin-3; D015848:Interleukin-5; D016178:Granulocyte-Macrophage Colony-Stimulating Factor