The role of L-selectin in leukocyte recruitment and functions.
Final Report Abstract
Leukocyte recruitment to the site of inflammation plays a pivotal role in host defence. Many studies focused on the different steps of the recruitment cascade, revealed that this process consists of different steps involving different of adhesion and homing receptors. Many studies focused on the effect of L-selectin signaling during inside-out signaling. In addition to the well-known function of L-selectin shedding to facilitate leukocyte migration, our studies identified a novel function of L-selectin shedding in supporting integrin-dependent outsidein signaling processes, resulting in increased neutrophil effector functions. Additionally, we revealed new detailed information about distinct functions of the different domains of L-selectin during neutrophil recruitment. Moesin and Ezrin were identified as important interaction partners of L-selectin and PSGL-1 after stimulating the cells with different stimuli. Further insights into how these processes are mechanistically regulated may offer new approaches to treat different types of infections or inflammatory diseases. While systemic administration of inhibitors or inducers of L-selectin shedding might pose detrimental risk for serious adverse events, future research will focus on the potential of organ-specific targeting of these defence mechanisms.
Publications
- (2019) L-selectin shedding affects bacterial clearance in the lung: a new regulatory pathway for integrin outside-in signaling. Blood 134 (17)1445–1457
Cappenberg, Anika; Margraf, Andreas; Thomas, Katharina; Bardel, Bernadette; McCreedy, Dylan A.; van Marck, Veerle; Mellmann, Alexander; Lowell, Clifford A.; Zarbock, Alexander
(See online at https://doi.org/10.1182/blood.2019000685) - The PSGL-1-L-selectin signaling complex regulates neutrophil adhesion under flow. J Exp Med. 2013 Oct 21;210(11):2171-80
Stadtmann A, Germena G, Block H, Boras M, Rossaint J, Sundd P, Lefort C, Fisher CI, Buscher K, Gelschefarth B, Urzainqui A, Gerke V, Ley K, Zarbock A
(See online at https://doi.org/10.1084/jem.20130664)
