Selective upregulation of a functional β<sub>7</sub> integrin on differentiating eosinophils

Lundahl, Joachim; Sehmi, Roma; Hayes, Lisa; Howie, Karen; Denburg, JA

doi:10.1034/j.1398-9995.2000.00574.x

Cited by 16 publications

(12 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sequential up‐regulation of the β integrins on progenitors has been the proposed mechanism to support the efflux of these cells from the bone marrow. Experiments that induced HL60 cells towards eosinophil differentiation showed a significant up‐regulation of functional β7 integrin expression coincident with down‐regulation of β1 integrin expression [65]. Subsequent studies confirmed and extended these findings, demonstrating up‐regulation of β7 integrin and down‐regulation of β1 and α5 integrins on cord blood progenitors during eosinophil differentiation [66], and thus suggesting the requirement for specific adhesion at distinct stages of cell maturation.…”

Section: Bone Marrowmentioning

confidence: 92%

Haemopoietic processes in allergic disease: eosinophil/basophil development

Gauvreau

Ellis

Denburg

2009

Clin Experimental Allergy

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Bone Marrowmentioning

confidence: 92%

Haemopoietic processes in allergic disease: eosinophil/basophil development

Gauvreau

Ellis

Denburg

2009

Clin Experimental Allergy

Self Cite

View full text Add to dashboard Cite

show abstract

“…Even though their role in eosinophil development remains unexplored, a4 integrin heterodimers are differentially regulated during terminal differentiation [16,17]. Here, we show that, in developing eosinophils, dexamethasone increases a4 integrin expression, and that treatments targeting a4 integrins induce dissociation and cytological maturation, supporting a regulatory role for a4 integrins during terminal differentiation.…”

Section: Introductionmentioning

confidence: 92%

“…In this study, we focused on a4 integrins, the bestcharacterized eosinophil integrins [11], because they were previously shown to influence the development of several haemopoietic lineages other than eosinophils, as follows: (a) a4b1 integrin mediates haemopoietic progenitor adhesion to VCAM-1-and fibronectin-expressing BM stroma [12]; (b) haemopoietic progenitors constitutively express a4b1 with high affinity [13]; (c) anti-a4b1 integrin antibodies block development of lymphoid and myeloid cells [12,14]; and (d) haemopoietic progenitor retention inside BM is a4 integrindependent [15]. Even though their role in eosinophil development remains unexplored, a4 integrin heterodimers are differentially regulated during terminal differentiation [16,17]. Here, we show that, in developing eosinophils, dexamethasone increases a4 integrin expression, and that treatments targeting a4 integrins induce dissociation and cytological maturation, supporting a regulatory role for a4 integrins during terminal differentiation.…”

Section: Introductionmentioning

confidence: 99%

Evidence for a regulatory role of α4 – integrins in the maturation of eosinophils generated from the bone marrow in the presence of dexamethasone

Gaspar−Elsas

Queto

Vasconcelos

et al. 2009

Clin Experimental Allergy

View full text Add to dashboard Cite

show abstract

“…An important mechanism for the selective recruitment of eosinophils to sites of allergic inflammation is by regulation of adhesion pathways such as β 2 integrin/ICAM-1, VLA-4/VCAM-1 and integrin β 7 [25,26,27]. DL has been shown to downregulate the adhesion molecule ICAM-1 [28, 29], which binds to its natural ligand LFA-1 present on eosinophils [30] and CD34+ progenitors [25, 26].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Desloratadine on Eosinophil/Basophil Progenitors and Other Inflammatory Markers in Seasonal Allergic Rhinitis: A Placebo-Controlled Randomized Study

Cyr¹,

Hayes²,

Crawford³

et al. 2005

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Background: Eosinophil/basophil (Eo/B) progenitors fluctuate in the peripheral circulation during seasonal allergen exposure in atopic subjects. Several drugs have been shown to modulate Eo/B progenitor levels in the peripheral blood but, to date, the possible effect of antihistamines on Eo/B progenitors has not been explored. Our objective was to evaluate whether the antihistamine desloratadine (DL) can modulate peripheral blood Eo/B progenitors or other markers of allergic inflammation. Methods: We performed a randomized double-blind placebo-controlled study on the effects of DL on peripheral blood Eo/B progenitors in subjects with symptomatic, seasonal allergic rhinitis during a ragweed pollen season. Forty-five subjects were randomized to treatment for 4 weeks with DL 20 mg daily or placebo. Results: The expected fall in the number of Eo/B progenitors from baseline to 2 weeks of treatment was seen in the placebo group [median drop of 1.0 colony-forming unit (CFU)/10⁶ cells], and was greater than in the DL group (median drop of 0.0 CFU/10⁶ cells) (p = 0.013). The change in histamine concentration per colony from baseline to 2 weeks of treatment was lower in the DL group (median decrease of 6.1 pg/colony) compared to placebo (median increase of 1.8 pg/colony) (p = 0.01). An increase in the nasal lavage eotaxin concentration from baseline to 4 weeks of treatment was statistically significant in the placebo group but not in the DL group. Eo/B CFU were not affected by varyingin vitro concentrations of DL. Conclusion: These results suggest that DL can modulate aspects of allergic inflammation in vivo through mechanisms other than simple blockade of H₁ histamine receptors.

show abstract

Selective upregulation of a functional β₇ integrin on differentiating eosinophils

Abstract: Our data show that protein synthesis-dependent upregulation of the functional beta7 integrin occurs under conditions when beta4 and beta1 integrins are fully expressed, indicating a sequential appearance of specific adhesion molecules on differentiating eosinophil progenitors.

Cited by 16 publications

References 58 publications

Haemopoietic processes in allergic disease: eosinophil/basophil development

Haemopoietic processes in allergic disease: eosinophil/basophil development

Evidence for a regulatory role of α4 – integrins in the maturation of eosinophils generated from the bone marrow in the presence of dexamethasone

The Effect of Desloratadine on Eosinophil/Basophil Progenitors and Other Inflammatory Markers in Seasonal Allergic Rhinitis: A Placebo-Controlled Randomized Study

Contact Info

Product

Resources

About

Selective upregulation of a functional β7 integrin on differentiating eosinophils

Abstract: Our data show that protein synthesis-dependent upregulation of the functional beta7 integrin occurs under conditions when beta4 and beta1 integrins are fully expressed, indicating a sequential appearance of specific adhesion molecules on differentiating eosinophil progenitors.

Cited by 16 publications

References 58 publications

Haemopoietic processes in allergic disease: eosinophil/basophil development

Haemopoietic processes in allergic disease: eosinophil/basophil development

Evidence for a regulatory role of α4 – integrins in the maturation of eosinophils generated from the bone marrow in the presence of dexamethasone

The Effect of Desloratadine on Eosinophil/Basophil Progenitors and Other Inflammatory Markers in Seasonal Allergic Rhinitis: A Placebo-Controlled Randomized Study

Contact Info

Product

Resources

About

Selective upregulation of a functional β₇ integrin on differentiating eosinophils