Nonreleasing basophils convert to releasing basophils by culturing with IL-3

Yamaguchi, Masao; Hirai, Koichi; Ohta, Ken; Suzuki, Katsuhiro; Kitani, Seiichi; Takaishi, Toshiaki; Itō, Kōji; Ra, Chisei; Morita, Yutaka

doi:10.1016/s0091-6749(96)70196-3

Cited by 66 publications

(35 citation statements)

References 31 publications

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“…Yamaguchi and colleagues reported that nonreleaser basophils recover secretory activity after incubation for 3 days or longer in IL-3 (5). Supporting this result, we show in Fig.…”

Section: Figuresupporting

confidence: 89%

“…Non-releaser basophils degranulate in response to stimuli such as N-formyl-methionyl-phenylalanine (fMet peptide), Ca 2ϩ ionophore, and PMA, suggesting that their lack of Ag-induced secretion results from the failure of early events specific to the Fc⑀RI signaling cascade (3)(4)(5)(6). Previous investigators established that Fc⑀RI expression and subunit composition are normal in nonreleaser basophils (3,5). We found that basophils from three nonreleaser donors lacked detectable levels of the Fc⑀RI-associated protein tyrosine kinase, Syk (6).…”

mentioning

confidence: 99%

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Multiple Defects in FcεRI Signaling in Syk-Deficient Nonreleaser Basophils and IL-3-Induced Recovery of Syk Expression and Secretion

Kepley

Youssef

Andrews

et al. 2000

The Journal of Immunology

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Human basophils respond to Ag-induced cross-linking of their high affinity IgE receptor, FcεRI, by releasing histamine and other mediators from granules, producing IL-4 and other cytokines and, as shown in this study, by forming membrane ruffles and showing increased very late Ag-4 (VLA-4)-mediated adhesion to VCAM-1-expressing target cells. We have identified five blood donors whose basophils lack detectable levels of the FcεRI-associated protein tyrosine kinase, Syk. Despite showing no obvious ultrastructural differences from normal basophils, nonreleaser basophils fail to form membrane ruffles, to show increased VLA-4-mediated adhesive activity, or to produce IL-4 in response to FcεRI cross-linking. Although Syk protein levels are suppressed in basophils from all five donors, Syk mRNA is consistently present. Furthermore, culturing nonreleaser basophils for 4 days with IL-3 restores Syk protein expression and FcεRI-mediated histamine release. Understanding the reversible suppression of Syk protein expression in nonreleaser basophils, and learning to replicate this property in patients with allergic inflammation could be a powerful and specific way to limit symptomatic disease.

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“…Yamaguchi and colleagues reported that nonreleaser basophils recover secretory activity after incubation for 3 days or longer in IL-3 (5). Supporting this result, we show in Fig.…”

Section: Figuresupporting

confidence: 89%

mentioning

confidence: 99%

Multiple Defects in FcεRI Signaling in Syk-Deficient Nonreleaser Basophils and IL-3-Induced Recovery of Syk Expression and Secretion

Kepley

Youssef

Andrews

et al. 2000

The Journal of Immunology

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“…This led to concern over the definition of a nonreleaser. Previously, we and others (3)(4)(5)(6)(7)(8)(9) have used different arbitrary cut points (usually 5-10%) to distinguish releasers from nonreleasers. We applied statistical methods to the entire data set to make an objective determination of the best cut point.…”

Section: Histamine Release Datamentioning

confidence: 99%

“…Changes in serum IL-3 levels have been proposed as a possible reason for cycling because in vitro culture with IL-3 can convert nonreleaser to releaser basophils (6,9). Estimates of IL-3 concentrations in serum are sparse, but values in the range of 5 pg/ml for normal subjects have been reported (19).…”

Section: Histamine Release Datamentioning

confidence: 99%

“…Basophils from a minority of subjects fail to secrete histamine, increase integrin-mediated adhesion, or produce IL-4 in response to FcRI cross-linking (2)(3)(4)(5)(6)(7)(8). The unresponsiveness of "nonreleaser" basophils has been linked to the increased proteasomal degradation of Syk, an essential tyrosine kinase in the FcRI-signaling cascade (5,9). Partial responses are recovered in nonreleaser basophils after prolonged IL-3 treatment, suggesting that changes in transcriptional regulation may underlie the differences between the releaser and nonreleaser phenotypes (6,9).…”

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confidence: 99%

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Histamine Release from the Basophils of Control and Asthmatic Subjects and a Comparison of Gene Expression between “Releaser” and “Nonreleaser” Basophils

Youssef

Schuyler²,

Gilmartin

et al. 2007

The Journal of Immunology

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Most human blood basophils respond to FcεRI cross-linking by releasing histamine and other inflammatory mediators. Basophils that do not degranulate after anti-IgE challenge, known as “nonreleaser” basophils, characteristically have no or barely detectable levels of the Syk tyrosine kinase. The true incidence of the nonreleaser phenotype, its relationship (if any) to allergic asthma, and its molecular mechanism are not well understood. In this study, we report statistical analyses of degranulation assays performed in 68 control and 61 asthmatic subjects that establish higher basal and anti-IgE-stimulated basophil degranulation among the asthmatics. Remarkably, 28% of the control group and 13% of the asthmatic group were nonreleasers for all or part of our 4-year long study and cycling between the releaser and nonreleaser phenotypes occurred at least once in blood basophils from 8 (of 8) asthmatic and 16 (of 23) control donors. Microarray analysis showed that basal gene expression was generally lower in nonreleaser than releaser basophils. In releaser cells, FcεRI cross-linking up-regulated >200 genes, including genes encoding receptors (the FcεRI α and β subunits, the histamine 4 receptor, the chemokine (C-C motif) receptor 1), signaling proteins (Lyn), chemokines (IL-8, RANTES, MIP-1α, and MIP-1β) and transcription factors (early growth response-1, early growth response-3, and AP-1). FcεRI cross-linking induced fewer, and quite distinct, transcriptional responses in nonreleaser cells. We conclude that “nonreleaser” and “cycler” basophils represent a distinct and reversible natural phenotype. Although histamine is more readily released from basophils isolated from asthmatics than controls, the presence of nonreleaser basophils does not rule out the diagnosis of asthma.

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Purification of Basophils from Peripheral Human Blood

Falcone

Gibbs

2020

Methods in Molecular Biology

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Nonreleasing basophils convert to releasing basophils by culturing with IL-3

Cited by 66 publications

References 31 publications

Multiple Defects in FcεRI Signaling in Syk-Deficient Nonreleaser Basophils and IL-3-Induced Recovery of Syk Expression and Secretion

Multiple Defects in FcεRI Signaling in Syk-Deficient Nonreleaser Basophils and IL-3-Induced Recovery of Syk Expression and Secretion

Histamine Release from the Basophils of Control and Asthmatic Subjects and a Comparison of Gene Expression between “Releaser” and “Nonreleaser” Basophils

Purification of Basophils from Peripheral Human Blood

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