Syk deficiency in nonreleaser basophils☆☆☆★

Kepley, Christopher L.; Youssef, Lama A.; Andrews, Ronald P.; Wilson, Bridget S.; Oliver, Janet M.

doi:10.1016/s0091-6749(99)70367-2

Cited by 156 publications

(140 citation statements)

References 14 publications

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“…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). Remarkably, Syk levels were normal in B cells, eosinophils, and neutrophils from the same donors.…”

mentioning

confidence: 62%

“…Reactions were terminated by dilution in ice-cold PBS and centrifugation, and histamine in cell pellets and supernatants was measured using an RIA (Alpco, Windham, NH), as described (6,8). Total histamine was measured in supernatants obtained by freeze thawing cell aliquots in PBS/ EDTA, followed by centrifugation at 10,000 ϫ g for 5 min to remove debris.…”

Section: Histamine Releasementioning

confidence: 99%

“…Expression of Lyn and Syk was measured in highly purified basophils (Ͼ99.9% pure; freshly isolated or IL-3 treated for 4 days) by Western blotting, as previously described (6,8).…”

Section: Western Blottingmentioning

confidence: 99%

“…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).…”

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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mentioning

confidence: 62%

Section: Histamine Releasementioning

confidence: 99%

“…Expression of Lyn and Syk was measured in highly purified basophils (Ͼ99.9% pure; freshly isolated or IL-3 treated for 4 days) by Western blotting, as previously described (6,8).…”

Section: Western Blottingmentioning

confidence: 99%

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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“…The absence of Syk expression led peripheral blood basophils to fail to degranulate in response to cross-linking the high affinity IgE receptor Fc⑀ receptor I (41). Also, TB1A2 cells, a Syk-negative variant of basophilic leukemia RBL-2H3 cells, failed to release histamine by the cross-linking system (22).…”

Section: Discussionmentioning

confidence: 99%

Protein-Tyrosine Kinase Syk Expressed in Human Nasal Fibroblasts and Its Effect on RANTES Production

Yamada

Fujieda

Yanagi

et al. 2001

The Journal of Immunology

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Fibroblasts, a rich source of chemokines, interact with eosinophils and play a key role in the pathogenesis of airway disease. RANTES is produced by fibroblasts to attract and activate eosinophils. LPS is known to induce RANTES and cause protein tyrosine phosphorylation. Nonreceptor protein tyrosine kinase Syk is widely expressed and an important role in intracellular signal transduction in hemopoietic cells. In the present study, we examined whether Syk was expressed in a number of primary human nasal polyp tissue-derived fibroblast lines and whether it played some role in cellular function. Syk proteins were expressed in human nasal fibroblasts, but the expression level varied. There were positive correlations between the level of Syk expression and RANTES production induced by LPS. Overexpression of wild-type Syk by gene transfer enhanced RANTES production from nasal fibroblasts stimulated with LPS. The decrease of Syk expression by the administration of Syk antisense inhibited RANTES production. These results suggest that Syk expression affects RANTES production in fibroblasts of nasal polyps.

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Mast Cells

Tsai

Galli

2011

Inflammation and Allergy Drug Design

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Syk deficiency in nonreleaser basophils☆☆☆★

Abstract: The absence of detectable Syk could explain the nonreleaser phenotype of basophils from some donors.

Cited by 156 publications

References 14 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

Protein-Tyrosine Kinase Syk Expressed in Human Nasal Fibroblasts and Its Effect on RANTES Production

Mast Cells

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