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Background Hematopoietic progenitor cells, especially those committed to the Eo/ B lineage, are known to contribute to allergic inflammation. Objective The aim of the present study was to investigate whether environmental factors are associated with changes in numbers of circulating Eo/ B progenitors at 1 year of age. Methods Peripheral blood from 60 1-year-old children enrolled in the LINA (Lifestyle and environmental factors and their Influence on Newborns Allergy risk) birth cohort was assessed for Eo/ B progenitor cells ( Eo/ B CFU) using standardized and validated methylcellulose assays. Frozen peripheral blood mononuclear cells ( PBMC) were cultured in the presence of IL-3, IL-5 or GM- CSF, and Eo/ B CFUs enumerated. Clinical outcomes and exposure to environmental tobacco smoke ( ETS) were documented by standardized questionnaires, and indoor volatile organic compound ( VOC) concentrations were assessed by passive sampling. Results Children with skin manifestations (atopic dermatitis or cradle cap) within the first year of life had higher numbers of circulating IL-3-, IL-5- or GM- CSF-stimulated Eo/ B CFUs ( P < 0.05) at 1 year. In children with cradle cap, a positive correlation was found between Eo/ B CFUs and exposure to ETS-related VOCs during pregnancy or at 1 year of age ( P < 0.05). Conclusions and Clinical Relevance This is the first demonstration that environmental exposures are positively associated with levels of circulating Eo/ B progenitors. The recruitment and differentiation of Eo/ B progenitors in response to environmental triggers may play a role in the development of skin manifestations during the first year of life. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents information on allergic rhinitis and its impact on asthma (ARIA). It informs that allergic rhinitis is a symptomatic disorder of the nose which is induced when exposed to allergen by an immunoglobulin E-mediated inflammation of the membranes lining the nose. It is noted that allergic rhinitis is a global health problem and the World Health Organization in the ARIA workshop updated guidelines concerning the disorder.

Increasing levels of proinflammatory cells, including eosinophils and basophils, are seen at the site of allergen challenge in allergic disease of the airways. Mechanisms for the recruitment of these cell types could involve either specific upregulation of adhesion molecule and chemoattraction, or the initiation of proliferation and differentiation of inflammatory cell progenitors derived from the bone marrow. In this study, we demonstrate, in two systems of eosinophilic–basophilic lineage-committed granulocytes of relative immaturity, that eosinophilic differentiation in vivo implies the induction of a distinct adhesion phenotype, characterized by the upregulation of β 7 integrin and downregulation of β 1 and α 5 integrins. Moreover, the eosinophilic differentiation induced an upregulation of complement receptor type 1 and type 3, and the expression was further enhanced upon a short-course in vitro activation with ionomycin. These data indicate a sequential alteration of disparate members of the integrin family during eosinophilic–basophilic differentiation, which may attribute to specific adhesion requirements at distinct stages of cell maturation. [ABSTRACT FROM AUTHOR]

Summary Eosinophils elaborate a number of proinflammatory mediators, including immunoregulatory cytokines and chemokines. Interleukin (IL)-4 and RANTES are important cytokines that have previously been shown to be expressed by mature eosinophils. We hypothesized that de novo synthesis of IL-4 and RANTES occurs in nascent eosinophils, leading to storage of newly produced proteins in crystalloid granule-like structures. Cytokine mRNA and protein expression were examined in cultured eosinophil colonies, which were derived from purified cord blood CD34+ cells and generated in semisolid media (methylcellulose) in the presence of recombinant human (rh)IL-3 and rhIL-5. Cytokine mRNA profiles were analysed by the reverse transcription–polymerase chain reaction (RT–PCR) to determine transcription of IL-4 and RANTES in cells on days 0, 7, 14, 21 and 28 of culture. The expression of translated cytokine products and granule major basic protein (MBP) was confirmed, from day 23 onwards, for colonies cultured in semisolid media, by immunofluorescent labelling and confocal laser-scanning microscopy (CLSM). We found that mRNA sequences encoding IL-4 and RANTES were expressed in freshly prepared, non-differentiated CD34+ cells. Furthermore, RANTES mRNA localized to carbol chromotrope 2R-positive colony cells, as assessed using in situ RT–PCR on day 21 of culture in semisolid media, and was found to gradually decrease (relative to β2-microglobulin) in rhIL-3- and rhIL-5-treated colony cells (comprising > 90% eosinophil-like cells) up to day 28. Immunoreactivity for IL-4 and RANTES co-localized with MBP in maturing colony eosinophils on day 23 of culture in semisolid media, as judged by CLSM. These results suggest that synthesis and storage of immunoregulatory cytokines, essential for processes associated with adaptive immunity, occurs in nascent eosinophils during their growth and differentiation. [ABSTRACT FROM AUTHOR]

Background: The sequence of adhesion-molecule expression during eosinophil differentiation remains unclear. Methods: We analyzed the surface expression of α4, β1, and β7 integrins and compared it to established myeloid developmental markers, using the eosinophilic cell line HL-60 clone 15, as well as cord and peripheral blood differentiation assays. Results: Cells induced to eosinophil differentiation by treatment with butyric acid, IL-5, and GM-CSF showed a significant upregulation of β7 integrin expression coincident with a marked upregulation of CD35 and attenuation of CD33 and β1 integrin expression. In addition, adhesion of induced HL-60 clone 15 cells to fibronectin was attenuated by a β7 integrin antibody. Conclusions: Our data show that protein synthesis-dependent upregulation of the functional β7 integrin occurs under conditions when α4 and β1 integrins are fully expressed, indicating a sequential appearance of specific adhesion molecules on differentiating eosinophil progenitors. [ABSTRACT FROM AUTHOR]