Haemopoietic processes in allergic disease: eosinophil/basophil development

Abstract

Haemopoietic myeloid progenitors contribute to the ongoing recruitment of pro-inflammatory cells, such as eosinophils and basophils (Eo/B), to target tissue sites in allergic diseases. It is apparent that the development of allergic inflammation is critically dependent on the ability of the bone marrow to support the proliferation, differentiation and mobilization of haemopoietic progenitors. The haemopoietic inductive microenvironment in the bone marrow is crucial for providing signals necessary for maintenance of progenitor populations at varying stages of lineage commitment and permitting these cells to circulate in the bloodstream. Progenitors demonstrate responsiveness to specific cytokines, which varies with stage of differentiation. Pro-inflammatory signals, Th2 cytokines in particular, generated following allergen challenge, can impact on haemopoietic progenitor differentiation and mobilization, leading to accelerated Eo/B production. Allergen inhalation by allergic asthmatics induces a time-dependent change in cytokine levels within the bone marrow compartment, influencing differentiation of Eo/B progenitors, as evidenced by the relationship between increased bone marrow IL-5 levels and Eo/B production. It is proposed that inhaled allergen induces trafficking of IL-5-producing T lymphocytes to the bone marrow, further promoting eosinophilopoiesis through IL-5R signalling. In this manner, Th2 lymphocyte trafficking from the airway may regulate events occurring in the bone marrow. Negative regulators of Eo/B differentiation, including Th1 cytokines, may prove to be important for restoring homeostasis. Eo/B progenitors are also altered in cord blood of infants at risk of atopy and asthma, offering a potential biomarker for, and raising the possibility that Eo/B progenitors are directly involved in the development of allergic disease. For example, changes in the expression of haemopoietic cytokine receptors on cord blood progenitor cells are associated with maternal allergic sensitization, atopic risk and its development, suggesting that haemopoietic processes underlying the allergic phenotype may begin to evolve in the perinatal period.

FLT-3 ITD Positive Acute Basophilic Leukemia with Rare Complex Karyotype Presenting with Acute Respiratory Failure: Case Report

“…Literature cites a case of mixed lineage eosinophil-basophil acute leukemia in a young female patient associating asthma [19]. T helper 2 lymphocytes trafficking from airways of asthmatic patients to the BM apparently induce up-regulation of interleukin-5 (IL-5) receptors on CD34+ progenitors, thus altering normal hematopoiesis and favoring IL-5 mediated expansion of eosinophil and basophil precursors [20]. However, it is virtually impossible to assess whether IL-5-induced modifications in the BM microenvironment of asthma patients might contribute to leukemogenesis and the subsequent basophilic and mastocytic differentiation in this particular case.…”

Distinctive Blood Eosinophilic Phenotypes and Cytokine Patterns in Eosinophilic Esophagitis, Inflammatory Bowel Disease and Airway Allergy

“…Eosinophils are produced in the bone marrow in response to GM-CSF, IL-3 and IL-5 [6] . An elevated plasma GM-CSF level was restricted to airway allergics, whereas IL-3 and IL-5 were raised in the plasma of EoE patients and airway allergics alike.…”

“…Eosinophils mature and differentiate in the bone marrow under the influence of granulocyte macropahge colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5 [6] . In the healthy state, newly produced eosinophils pass via the bloodstream to their final destination, primarily the gut mucosa, but also to the thymus, spleen and lymph nodes [7] .…”

Common genetic factors for hematological traits in Humans

“…Both are known to be involved in the regulation of allergic reactions. 48,49 Basophils are the rarest of the major WBC subtypes and their role in host immunity has been less clear, although recent studies have indicated that they essentially provide unique functions including acting as antigen- 40 presenting cells that promote T helper cell 2-associated allergic responses. 48,50 Associations at the DARC locus Genetic association studies on WBC-related hematological traits firstly focused on the ethnic differences in total WBC counts between European and African populations 11 that could not be explained by known non-genetic factors (Table 1).…”