The role of the Tec kinase "Bruton´s Tyrosine Kinase" (Btk) in integrin activation and leukocyte recruitment
Final Report Abstract
Sterile inflammation induces the release of pro-inflammatory molecules including formylated peptides. These molecules trigger different signaling pathways leading to the recruitment of leukocytes. This process has to be tightly balanced since inadequate activation can lead to an overwhelming immune answer which results in tissue destruction and increased inflammation. To understand the mechanism behind this appropriate leukocyte recruitment can facilitate the development of drugs which are able to influence the immune response or to support wound healing and prevent tissue damage. We identified a signaling complex which is crucially involved in the immune response following sterile liver injury. We demonstrated that the src kinase Hck, Wiskott-Aldrich syndrome protein, Btk and Phospholipase Cγ2 are part of a signaling cascade responding to the released formylated peptides due to sterile liver injury. We investigated the underlying mechanism and showed that formylated peptides trigger Mac1 activation. This integrin is responsible for several leukocyte functions like adhesion, crawling, and transmigration, and is therefore indispensable for appropriate leukocyte recruitment. We also investigated the contribution of Btk in other leukocyte functions, like phagocytosis and superoxide release, which are also part of the immune response. Here, we demonstrated that Btk is also part of these signaling pathways, underlining its important role in the whole process.
Publications
- The Neutrophil Btk Signalosome Regulates Integrin Activation during Sterile Inflammation. Immunity. 2016 Jan 19;44(1):73-87
Volmering S, Block H, Boras M, Lowell CA, Zarbock A
(See online at https://doi.org/10.1016/j.immuni.2015.11.011)
