title: Bruton's tyrosine kinase is not essential for LPS-induced activation of human monocytes.
abstract: BACKGROUND
  X-linked agammaglobulinemia (XLA) is characterized by impaired B-cell differentiation caused by mutations in the Bruton's tyrosine kinase (Btk) gene. The natural disease model, the X-linked immunodeficiency mouse, shows a less severe phenotype, indicating a different requirement of Btk in human and mouse B cells. Btk is also expressed in the myeloid line and participates in LPS signaling. Deficient oxidative burst and myeloid differentiation have been reported in the X-linked immunodeficiency mouse, but the precise mechanism and relevance of Btk activity in human monocytes is poorly understood.
  
  
  OBJECTIVE
  The apparent absence in XLA of clinical manifestations of myeloid deficiency prompted us to explore the relevance of complete Btk absence in human myeloid cells.
  
  
  METHODS
  Seven patients with XLA with BTK mutations conditioning a null protein expression were included in the study. Monocyte LPS-induced mitogen-activated protein kinase activation, TNF-alpha and IL-6 production in monocytes, and oxidative burst in monocytes and granulocytes were analyzed by means of flow cytometry.
  
  
  RESULTS
  We show that in response to LPS, Btk-null monocytes from patients with XLA induce early mitogen-activated protein kinase activation and intracellular TNF-alpha and IL-6 production with the same intensity as cells from age- and sex-matched control subjects. In addition, the oxidative burst in response to LPS and other stimulants was completely normal in Btk-null monocytes and neutrophils.
  
  
  CONCLUSIONS
  Our results indicate that Btk is not essential for early LPS signaling in human monocytes and that different Btk dependency might exist between human and mouse myeloid cells.
  
  
  CONCLUSIONS
  These findings provide a better understanding of XLA, and they show the differences between human XLA and murine Xid models.
authors.affiliation: Immunology Unit, University Hospital "La Paz," Madrid, Spain. rperez.hulp@salud.madrid.org
authors.forename: Rebeca
authors.initials: R
authors.lastname: Pérez de Diego
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Granados
authors.forename: Maite
authors.initials: M
authors.lastname: Pozo
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez
authors.forename: Prado
authors.initials: P
authors.lastname: Sabina
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferreira
authors.forename: Gumersindo
authors.initials: G
authors.lastname: Fontan
authors.forename: Maria Cruz
authors.initials: MC
authors.lastname: García-Rodríguez
authors.forename: Susana
authors.initials: S
authors.lastname: Alemany
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D000818:Animals; D002478:Cells, Cultured; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D007223:Infant; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse; D020928:Mitogen-Activated Protein Kinases