The effects of Bruton tyrosine kinase inhibition on chemotaxis and superoxide generation in human neutrophils.
J Clin Immunol
; 34(5): 555-60, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24771458
ABSTRACT
PURPOSE:
The role of the Bruton tyrosine kinase (Btk) protein in neutrophil function has been evaluated using neutrophils from healthy volunteers after incubation with a Btk inhibitor, leflunomide metabolite analog (LFM-A13), suggesting an important role for Btk in neutrophil function. We sought to determine the role of Btk protein on neutrophil superoxide generation and chemotaxis stimulated by N-formyl-methionine-leucine-phenylalanine (fMLP).METHODS:
Chemotaxis was assayed on agarose gel and superoxide generation by cytochrome C reduction. The affects of LFM-A13 on chemotaxis and superoxide generation in unstimulated and fMLP stimulated neutrophils were studied in Btk deficient neutrophils from XLA patients compared with matched controls analyzed simultaneously.RESULTS:
Chemotaxis and stimulated superoxide production were similar in the normal and Btk deficient neutrophils and were similarly inhibited by LFM-A13. In one patient, LFMA13 had no effect on superoxide generation in Btk deficient neutrophils up to a concentration of 25 microM, while inhibited superoxide production by control neutrophils.CONCLUSIONS:
Our results suggest that Btk does not have a specific role in neutrophil fMLP-stimulated superoxide generation and chemotaxis since these activities were similarly inhibited by LFM-A13 in Btk deficient and normal neutrophils. The lack of superoxide generation following Btk inhibition by LFM-A13 in Btk deficient neutrophils from one patient may suggest some heterogeneity in the role of Btk in fMLP induced neutrophil superoxide generation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Tirosina Quinasas
/
Superóxidos
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Agammaglobulinemia
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Enfermedades Genéticas Ligadas al Cromosoma X
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Inhibidores de Proteínas Quinasas
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Amidas
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Neutrófilos
/
Nitrilos
Tipo de estudio:
Observational_studies
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Humans
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Infant
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Male
Idioma:
En
Revista:
J Clin Immunol
Año:
2014
Tipo del documento:
Article