Kinetics of Bone Marrow Eosinophilopoiesis and Associated Cytokines after Allergen Inhalation

Abstract

Allergen inhalation is associated with increased eosinophil/basophil progenitors in bone marrow 24 hours after allergen inhalation. This study examined the kinetics of eosinophilopoiesis in dual (n = 14), compared with isolated early, responders (n = 12). Dual responders, in contrast to isolated early responders, develop significant sputum and blood eosinophilia and prolonged airway hyperresponsiveness. Bone marrow aspirates were taken before and 5, 12, 24, and 48 hours after allergen inhalation. In dual responders, increases in interleukin (IL)-3-responsive progenitors were detected as early as 5 hours after allergen inhalation, and IL-5-responsive progenitors were detected at 12 and 24 hours. No changes were detected in isolated early responders. Bone marrow IL-5 protein levels increased at 12 and 24 hours in dual responders only and these increases correlated with increases in IL-5-responsive progenitors. In addition, bone marrow IFN-gamma levels increased in dual responders at 48 hours. These data demonstrate that, in dual responders, there is allergen-induced activation of an eosinophilopoietic process that is rapid and sustained, and a relationship between increased bone marrow IL-5 levels and increased eosinophil production. We propose that after allergen inhalation, time-dependent changes in cytokine levels in the bone marrow control differentiation of eosinophil/basophil progenitors.

Small interfering RNA against interleukin-5 decreases airway eosinophilia and hyper-responsiveness

“…However, the number of airway eosinophils in SEC4-treated mice reduced only about 45% compared to that of SECneg-treated mice. This implies that other cytokines, such as IL-3 24 and granulocyte-macrophage colony-stimulating factor, 25 might also be important in eosinophil survival and persistence in tissues.…”

Análisis de la curva flujo-volumen en niños y adolescentes con rinitis alérgica sin asma

“…Los estudios precedentes detectaron un incremento de la progenie de eosinófilos y de la expresión de citocinas afines (IL-5) en la médula ósea y la sangre periférica luego de la prueba de provocación nasal con alérgenos, 21,22 lo que indica que probablemente la eosinofilia hemática esté más relacionada con la inflamación sistémica que la eosinofilia nasal y la IgE sérica, con impacto en la vía aérea intratorácica y la consecuente afectación subclínica de la función pulmonar. La influencia del IMC sobre las variables funcionales pulmonares de nuestros pacientes es más difícil de explicar.…”

Airway exposure to staphylococcal enterotoxin A potentiates allergen-induced bone marrow eosinophilia and trafficking to peripheral blood and airways

“…Allergic stimulation elevates the serum levels of IL-5 that further enhances the expression of IL-5 receptor (IL-5R1), expanding to 10-to 20-fold (or even greater) the BM eosinophil progenitor, thus promoting their differentiation into mature cells for release into the peripheral blood (41). Furthermore, increased number of CD34 ϩ /IL-5R␣ ϩ and CD34 ϩ cells expressing the eotaxin receptor CCR3 (CD34 ϩ /CCR3 ϩ cells) was observed in BM during allergen challenge in mice (9,40,39). Eotaxin is a CC-chemokine responsible for selective eosinophil chemotaxis and transendothelial migration in airways of allergic subjects ϩ /VLA-4 ϩ (C) expression in bone marrow eosinophils of OVA-challenged mice.…”