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Publication : The Neutrophil Btk Signalosome Regulates Integrin Activation during Sterile Inflammation.

First Author  Volmering S Year  2016
Journal  Immunity Volume  44
Issue  1 Pages  73-87
PubMed ID  26777396 Mgi Jnum  J:259937
Mgi Id  MGI:6141129 Doi  10.1016/j.immuni.2015.11.011
Citation  Volmering S, et al. (2016) The Neutrophil Btk Signalosome Regulates Integrin Activation during Sterile Inflammation. Immunity 44(1):73-87
abstractText  Neutrophils are recruited from the blood to sites of sterile inflammation, where they are involved in wound healing but can also cause tissue damage. During sterile inflammation, necrotic cells release pro-inflammatory molecules including formylated peptides. However, the signaling pathway triggered by formylated peptides to integrin activation and leukocyte recruitment is unknown. By using spinning-disk confocal intravital microscopy, we examined the molecular mechanisms of leukocyte recruitment to sites of focal hepatic necrosis in vivo. We demonstrated that the Bruton''s tyrosine kinase (Btk) was required for multiple Mac-1 activation events involved in neutrophil recruitment and functions during sterile inflammation triggered by fMLF. The Src family kinase Hck, Wiskott-Aldrich-syndrome protein, and phospholipase Cgamma2 were also involved in this pathway required for fMLF-triggered Mac-1 activation and neutrophil recruitment. Thus, we have identified a neutrophil Btk signalosome that is involved in a signaling pathway triggered by formylated peptides leading to the selective activation of Mac-1 and neutrophil recruitment during sterile inflammation.
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