The effects of Bruton tyrosine kinase inhibition on chemotaxis and superoxide generation in human neutrophils

Arnon Broides, Nurit Hadad, Jacov Levy, Rachel Levy

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


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.

Original languageEnglish
Pages (from-to)555-560
Number of pages6
JournalJournal of Clinical Immunology
Issue number5
StatePublished - 1 Jan 2014


  • Bruton tyrosine kinase
  • chemotaxis
  • neutrophil
  • superoxide

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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