A neutrophil-centric view of chemotaxis

Abstract Neutrophils are key players of the innate immune system, that are involved in coordinating the initiation, propagation and resolution of inflammation. Accurate neutrophil migration (chemotaxis) to sites of inflammation in response to gradients of chemoattractants is pivotal to these roles. Binding of chemoattractants to dedicated G-protein-coupled receptors (GPCRs) initiates downstream signalling events that promote neutrophil polarisation, a prerequisite for directional migration. We provide a brief summary of some of the recent insights into signalling events and feedback loops that serve to initiate and maintain neutrophil polarisation. This is followed by a discussion of recent developments in the understanding of in vivo neutrophil chemotaxis, a process that is frequently referred to as ‘recruitment’ or ‘trafficking’. Here, we summarise neutrophil mobilisation from and homing to the bone marrow, and briefly discuss the role of glucosaminoglycan-immobilised chemoattractants and their corresponding receptors in the regulation of neutrophil extravasation and neutrophil swarming. We furthermore touch on some of the most recent insights into the roles of atypical chemokine receptors (ACKRs) in neutrophil recruitment, and discuss neutrophil reverse (transendothelial) migration together with potential function(s) in the dissemination and/or resolution of inflammation.