Comparative effects of basophil-directed growth factors

Yoshimura-Uchiyama, Chitose; Yamaguchi, Masao; Nagase, Hiroyuki; Fujisawa, Takao; Ra, Chisei; Matsushima, Kouji; Iwata, Tadahisa; Igarashi, Takashi; Yamamoto, Kazuhiko; Hirai, Koichi

doi:10.1016/s0006-291x(03)00153-0

Cited by 33 publications

(43 citation statements)

References 19 publications

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“…Close to 60% of basophils stayed alive after 3 days in culture when almost all neutrophils and eosinophils died. Among the 3 GM-CSF family members known to regulate basophil functions, [41][42][43][44][45] only IL-3 efficiently protected basophils from apoptosis, whereas GM-CSF and IL-5 had no significant effect. IL-3, IL-5, and GM-CSF all prolonged the life span of eosinophils, whereas only GM-CSF enhanced neutrophil survival.…”

Section: Human Blood Basophils Are Long-lived Cells Expressing High Lmentioning

confidence: 99%

“…Caspase 3 activation was measured as a marker of early stages of apoptosis. Figure 2A shows that, besides IL-3, none of the 11 cytokines listed, including the basophil priming factors, IL-5, GM-SCF, and NGF, [41][42][43][44][45] efficiently prevented the generation of active caspase 3 and PARP/ Bcl-2 cleavage. Analysis of cell apoptosis using annexin V staining (not shown) confirmed that, with the exception of IL-3, the cytokines tested exert no or minimal effects on basophil life span.…”

Section: Il-3 Is a Unique Basophil Survival Factor That Induces A Rapmentioning

confidence: 99%

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IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils

Didichenko

Spiegl

Brunner

et al. 2008

Blood

107

100

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IntroductionApoptosis of granulocytes and subsequent clearance of apoptotic cells are important processes for the successful resolution of acute and chronic inflammation. Basophils represent the least abundant granulocyte population and are considered as key effector cells in Th2-type, IgE-associated allergic disorders as well as in protective immune responses to helmints. Pro-inflammatory and immunomodulatory activities of basophils include secretion of histamine and the lipid mediator leukotriene C 4 as well as rapid production of interleukin-4 (IL-4) and IL-13, Th2-type cytokines crucial for the development of allergy and asthma. Positive regulators of basophil mediator release and cytokine production have been described, whereas attempts to find negative regulators of basophil cellular functions have been unsuccessful. Therefore, the modulation of basophil apoptosis probably has a particularly high impact on the outcome of allergic inflammation.Cytokines of granulocyte-macrophage colony-stimulating factor (GM-CSF) subfamily (GM-CSF, IL-5, and IL-3) support granulocyte survival in a granulocyte-type-restricted manner. [1][2][3][4][5][6] Modulation of neutrophil and eosinophil apoptosis mediated by these cytokines has been suggested to rely on the up-regulation of antiapoptotic proteins of the Bcl-2 family, such as Bcl-2, Bcl-X L , Mcl-1 and A1, 7-9 as well as IAP family proteins. [10][11][12] With regards to signaling pathways, Janus kinase (JAK)/signal transducer and activator of transcription 3 and 5 (Stat3/Stat5), phosphatidylinositol 3-kinase (PI3-kinase), as well as p38-mitogen-activated protein kinase (MAPK) have been implicated in the regulation of neutrophil and eosinophil apoptosis by GM-CSF, IL-5, and IL-3. [13][14][15][16][17][18][19] Although previous studies showed that IL-3 prolongs the life span of basophils, 5,6 there is a complete lack of knowledge about the proteins and the mechanisms that regulate spontaneous and cytokineenhanced survival of basophils. A single report suggested a requirement of PI3-kinase signaling for IL-3-mediated basophil survival. 6 The mechanisms of IL-3 signaling and the involvement of downstream targets regulating cell proliferation and survival have been most thoroughly studied in leukemic human cell lines and IL-3-dependent cell lines from genetically manipulated mice. Most papers highlight the requirement of the PI3-kinase/Akt (PKB) signaling pathway and mainly differ in their interpretations about the relative importance of downstream targets, such as Bad, FOXO3, and NF-B. 20-24 These findings cannot always be transferred to human basophils or other nondividing leukocytes because the regulation of survival strongly depends on the cellular background. Furthermore, the mechanisms regulating proliferation or apoptosis are difficult to distinguish in proliferating cells, and transformed cell lines may display disturbed signaling pathways. It is thus necessary to study primary blood basophils ex vivo to understand the mechanisms regulating their survival, despite inhe...

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Section: Human Blood Basophils Are Long-lived Cells Expressing High Lmentioning

confidence: 99%

Section: Il-3 Is a Unique Basophil Survival Factor That Induces A Rapmentioning

confidence: 99%

IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils

Didichenko

Spiegl

Brunner

et al. 2008

Blood

107

100

View full text Add to dashboard Cite

show abstract

“…CD11b expression on basophils was analyzed by staining with PE-conjugated antihuman-CD11b mAb (Bear1; Coulter Immunotech) and FITC-conjugated anti-human IgE Ab (BioSource International) for 60 min on ice. Stained cells were analyzed using a FACSCalibur (BD Biosciences), and the median values of fluorescence intensity were converted to the number of molecules of equivalent soluble fluorochrome units using a quantum fluorescent microbead standard for PE (Sigma-Aldrich), as described previously (24). FITC-conjugated anti-CD3 (BW264/56), FITC-conjugated anti-CD14(TUK4),FITC-conjugatedanti-CD16(VEP13),FITC-conjugatedanti-CD19 (LT19), and FITC-conjugated anti-CD123 (AC145) mAbs were purchased from Miltenyi Biotec.…”

Section: Flow Cytometrymentioning

confidence: 99%

Down-Regulation of Basophil Function by Human CD200 and Human Herpesvirus-8 CD200

Shiratori

Yamaguchi

Suzukawa

et al. 2005

The Journal of Immunology

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103

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Human and rodent CD200 are recognized by the inhibitory CD200R, and these molecules play an important role in the regulation of the immune system. Several viruses, such as human herpesvirus-6 (HHV-6), HHV-7, and HHV-8, possess a CD200 homologue, suggesting that these viruses regulate the immune response via CD200R. In this study, we analyzed the effect of human CD200 and the viral CD200 homologues on human CD200R-expressing cells. We found that human CD200R is predominantly expressed on basophils in amounts higher than on other human peripheral blood leukocytes. Furthermore, the viral CD200 homologues as well as human CD200 were recognized by human CD200R, and the activation of basophils was down-regulated by these CD200 proteins. These results suggested that CD200R is an important regulatory molecule of basophil activation. In addition, the presence of CD200 homologues on several viruses suggests a potentially unique relationship between basophil function and viral infection.

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“…Especially IL-3, IL-5, and GM-CSF, which are known as important basophilopoietins, are strong activators of mature basophils. We and others have demonstrated that these cytokines potentiate peripheral blood basophils by prolonging their lifespan (11), upregulating certain surface receptors, and enhancing their degranulation (12,13), adhesion (14), cytokine synthesis (15), and migration (11,16,17). Our knowledge concerning the regulatory mechanisms of basophil functions continues to expand.…”

mentioning

confidence: 98%

An IL-1 Cytokine Member, IL-33, Induces Human Basophil Activation via Its ST2 Receptor

Suzukawa

Iikura

Koketsu

et al. 2008

The Journal of Immunology

Self Cite

282

231

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Basophils are thought to play pivotal roles in allergic inflammation through rapid release of chemical mediators in addition to sustained production of Th2 cytokines, including IL-4. A newly identified cytokine, IL-33, has been recognized as one of the key cytokines enhancing Th2-balanced immune regulation through its receptor, ST2. The present study was conducted to elucidate whether IL-33 acts directly on, and affects the functions of, human basophils. Real-time PCR analysis showed that basophils express transcripts for ST2. The expression levels were significantly higher compared with eosinophils and neutrophils, and treatment with IL-33 significantly up-regulated basophil ST2 mRNA expression. Expressions of IL-4 and IL-13 mRNA were also up-regulated by IL-33, and there was also enhanced secretion of IL-4 protein. IL-33 increased the surface levels of basophil CD11b expression and enhanced basophil adhesiveness. Although IL-33 failed to directly induce degranulation or attract basophils, it exerted priming effects on basophils. It enhanced degranulation in response to IgE-crosslinking stimulus and also enhanced basophil migration toward eotaxin without changing surface CCR3. Also, IL-33 synergistically enhanced IL-4 production and CD11b expression by IL-3-stimulated basophils. Neutralization using Ab specific for ST2 significantly diminished the enhancing effects of IL-33 on both basophil CD11b expression and migration toward eotaxin, indicating that IL-33 signals via ST2 expressed on basophils. This study revealed that IL-33 potently regulates migration and activation of human basophils. IL-33 may be a key cytokine in the pathogenesis of Th2-dominant inflammation by acting not only on lymphocytes but also on effector cells such as basophils.

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Comparative effects of basophil-directed growth factors

Cited by 33 publications

References 19 publications

IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils

IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils

Down-Regulation of Basophil Function by Human CD200 and Human Herpesvirus-8 CD200

An IL-1 Cytokine Member, IL-33, Induces Human Basophil Activation via Its ST2 Receptor

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