Pleiotropic consequences of Bruton tyrosine kinase deficiency in myeloid lineages lead to poor inflammatory responses.
Bruton tyrosine kinase (Btk), a non-receptor-associated tyrosine kinase of the Tec family, appears to participate in many myeloid cell functions. We show that macrophages from X-linked immunodeficient (XID) mice lacking functional Btk cannot generate efficient bursts of reactive oxygen intermediates (ROIs). The induction of apoptotic cell death by inflammatory stimuli is also enhanced in XID macrophages. Phagocytosis of bacterial particles is only marginally affected in them. In vivo, XID mice show reduced severity of inflammatory diseases in models of experimental autoimmune encephalomyelitis (EAE), dextran sulfate sodium (DSS)-induced colitis, and carrageenan-induced acute edema. Also, polymorphonuclear neutrophil granulocytes (PMNs) in XID mice show poor ROI and nitric oxide (NO) induction, along with a reduction in PMN recruitment to peritoneal inflammation. XID mice show reduction in PMN numbers in peripheral blood, and their bone marrow shows a reduction in the numbers of both monocytic and granulocytic lineages, extending to the earliest progenitor populations. Thus, Btk is likely to play a significant role at multiple points during the development and functioning of the myeloid lineages, affecting the outcome of many infectious as well as noninfectious inflammatory events in vivo.
Mangla
Anita
A
Anna George, or Satyajit Rath, National Institute of Immunology, Aruna Asaf Ali Road, New Delhi 110067, India.
Khare
Anupriya
A
Vineeth
Varanasi
V
Panday
Nagesh Narayan
NN
Mukhopadhyay
Asok
A
Ravindran
Balachandran
B
Bal
Vineeta
V
George
Anna
A
Rath
Satyajit
S
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000473:pathology; D002452:Cell Count; D019070:Cell Lineage; D007249:Inflammation / Q000201:enzymology* / Q000473:pathology; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D022423:Myeloid Cells / Q000201:enzymology* / Q000473:pathology; D009504:Neutrophils / Q000201:enzymology / Q000473:pathology; D010587:Phagocytosis; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse