Neutrophil breaching of venular walls in vivo: Mode, mechanisms and pathogenesis

Within our laboratory we investigate neutrophil trafficking, most notably neutrophil-venular wall interactions as analysed by confocal intravital microscopy. The application of this methodology to quantitative imaging of physiological reactions has shed much light on our understanding of the mode, mechanisms and dynamics of neutrophil endothelial cell interactions, and the previously un-explored response of neutrophil-pericyte interactions. Furthermore, analysis of pathological settings, such as ischemia-reperfusion injury has identified numerous aberrant neutrophil behaviours, including neutrophils exhibiting reverse motility at the level of endothelial cell junctions and moving from the basolateral to apical aspect of the endothelium. Importantly, this response offers a new paradigm for how a local inflammatory response is disseminated to remote organs. Overall our studies have demonstrated that direct and rigorous analysis of neutrophil-vessel wall behaviours and dynamics are likely to identify novel and disease-specific phenomena that could promote a change in thinking towards development of new therapeutic strategies