Allergen stimulates bone marrow CD34+ cells to release IL‐5 in vitro; a mechanism involved in eosinophilic inflammation?

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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.

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