Syk expression in peripheral blood leukocytes, CD34+ progenitors, and CD34-derived basophils

Ishmael, Susan S.; MacGlashan, Donald W.

doi:10.1189/jlb.0509336

Cited by 27 publications

(53 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…study to measure histamine content in murine basophils collected in the lung. The histamine content (0.12 pg·per cell) was lower than that in human peripheral blood basophils, which possessed 1.1 pg·per cell (Patella et al, 1995a) or 1.3 pg per·cell (Ishmael and MacGlashan, 2010) of histamine. Schneider et al (1999) reported that murine basophil precursors may have histidine decarboxylase and produce histamine.…”

Section: Figurementioning

confidence: 90%

Roles of basophils and mast cells infiltrating the lung by multiple antigen challenges in asthmatic responses of mice

Nabe

Matsuya

Akamizu

et al. 2013

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSEMast cell hyperplasia has been observed in the lungs of mice with experimental asthma, but few reports have studied basophils. Here, we attempted to discriminate and quantify mast cells and basophils in the lungs in a murine asthma model, determine if both cells were increased by multiple antigen challenges and assess the roles of those cells in asthmatic responses. EXPERIMENTAL APPROACHSensitized Balb/c mice were intratracheally challenged with ovalbumin four times. Mast cells and basophils in enzymatically digested lung tissue were detected by flow cytometry. An anti-FceRI monoclonal antibody, MAR-1, was i.p. administered during the multiple challenges. KEY RESULTSThe numbers of both mast cells (IgE + C-kit + ) and basophils (IgE + C-kit -CD49b + ) increased in the lungs after three challenges. Treatment with MAR-1 completely abolished the increases; however, a late-phase increase in specific airway resistance (sRaw), and airway eosinophilia and neutrophilia were not affected by the treatment, although the early-phase increase in sRaw was suppressed. MAR-1 reduced antigen-induced airway IL-4 production. Basophils infiltrating the lung clearly produced IL-4 after antigen stimulation in vitro; however, histamine and murine mast cell protease 1 were not increased in the serum after the challenge, indicating that mast cell activation was not evoked. CONCLUSION AND IMPLICATIONSBoth mast cells and basophils infiltrated the lungs by multiple intratracheal antigen challenges in sensitized mice. Neither mast cells nor basophils were involved in late-phase airway obstruction, although early-phase obstruction was mediated by basophils. Targeting basophils in asthma therapy may be useful for an early asthmatic response.

show abstract

Section: Figurementioning

confidence: 90%

Roles of basophils and mast cells infiltrating the lung by multiple antigen challenges in asthmatic responses of mice

Nabe

Matsuya

Akamizu

et al. 2013

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Our previous study (and all subsequent studies including this one) also demonstrated that the response to a non-IgE-dependent stimulus, FMLP, was not changed 10 , suggesting that the effects of omalizumab are restricted to IgE-mediated signaling steps. It has also been suggested that studies of sustained aggregation during the maturation of basophils from CD34 progenitors might be applicable to this situation 31 . In previous studies, sustained aggregation during maturation resulted in “basophils” that expressed normal levels of histamine, granules and FcεRI but showed reduced syk expression.…”

Section: Discussionmentioning

confidence: 99%

Omalizumab increases the intrinsic sensitivity of human basophils to IgE-mediated stimulation

MacGlashan

Saini

2013

Journal of Allergy and Clinical Immunology

Self Cite

View full text Add to dashboard Cite

Background Treatment of allergic patients with omalizumab results in a paradoxical increase in their basophil histamine release response, ex vivo, to crosslinking anti-IgE antibody. It is not known whether this change in response is associated with an increase in intrinsic cellular sensitivity, which would be a paradoxical response. Objective To determine if the increase in response to anti-IgE Ab is a reflection of an increased cellular sensitivity, expressed as molecules of antigen-specific IgE per basophil required to produce a 50% of maximal response. Methods Patients were treated with omalizumab or placebo agent for 12 weeks (NCT01003301 at ClinicalTrials.gov) and the metric of basophil sensitivity was assessed at 4 time points, baseline, 6–8 weeks, 12 weeks (after which treatment stopped) and 24 weeks (12 weeks after the end of treatment). Results As observed previously, treatment with omalizumab resulted in a marked increase in the maximal histamine release induced by crosslinking anti-IgE Ab. This change was accompanied by a marked shift in intrinsic basophil sensitivity, ranging from 2.5 to 125 fold, with an average of 6 fold at the midpoint of the treatment to 12 fold after 12 weeks. The magnitude of the increase in cellular sensitivity was inversely related to the starting sensitivity or the starting maximum histamine release. The increased cellular sensitivity also occurred when using LTC4 secretion as a metric of the basophil response. 12 weeks after the end of treatment, cellular sensitivity was found to shift towards the baseline level although the return to baseline was not yet complete at this time point. Conclusions Treatment with omalizumab results in a markedly increased sensitivity of basophils to IgE-mediated stimulation, in terms of the number of IgE molecules required to produce a given response. These results provide a better quantitative sense of the phenotypic change that occurs in basophils during omalizumab treatment which has implications both mechanistic and clinical.

show abstract

“…+ cells predominately generates basophils but can generate mast cells to a lesser degree (50,53,54). Following 2 wk in culture, ∼51% of cells expressed basophil surface marker phenotypes (CD203c (Fig.…”

Section: Il-3-mediated Differentiation Of Human Cd34mentioning

confidence: 99%

Comprehensive population-based genome sequencing provides insight into hematopoietic regulatory mechanisms

Guo

Nandakumar

Ulirsch

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Genetic variants affecting hematopoiesis can influence commonly measured blood cell traits. To identify factors that affect hematopoiesis, we performed association studies for blood cell traits in the population-based Estonian Biobank using highcoverage whole-genome sequencing (WGS) in 2,284 samples and SNP genotyping in an additional 14,904 samples. Using up to 7,134 samples with available phenotype data, our analyses identified 17 associations across 14 blood cell traits. Integration of WGS-based fine-mapping and complementary epigenomic datasets provided evidence for causal mechanisms at several loci, including at a previously undiscovered basophil countassociated locus near the master hematopoietic transcription factor CEBPA. The fine-mapped variant at this basophil count association near CEBPA overlapped an enhancer active in common myeloid progenitors and influenced its activity. In situ perturbation of this enhancer by CRISPR/Cas9 mutagenesis in hematopoietic stem and progenitor cells demonstrated that it is necessary for and specifically regulates CEBPA expression during basophil differentiation. We additionally identified basophil count-associated variation at another more pleiotropic myeloid enhancer near GATA2, highlighting regulatory mechanisms for ordered expression of master hematopoietic regulators during lineage specification. Our study illustrates how population-based genetic studies can provide key insights into poorly understood cell differentiation processes of considerable physiologic relevance.genome sequencing | GWAS | basophils | hematopoiesis | CEBPA

show abstract

Syk expression in peripheral blood leukocytes, CD34+ progenitors, and CD34-derived basophils

Cited by 27 publications

References 37 publications

Roles of basophils and mast cells infiltrating the lung by multiple antigen challenges in asthmatic responses of mice

Roles of basophils and mast cells infiltrating the lung by multiple antigen challenges in asthmatic responses of mice

Omalizumab increases the intrinsic sensitivity of human basophils to IgE-mediated stimulation

Comprehensive population-based genome sequencing provides insight into hematopoietic regulatory mechanisms

Contact Info

Product

Resources

About