Neutrophil microdomains: linking heterocellular interactions with vascular injury

Abstract

Neutrophil infiltration is an important feature in inflammatory scenarios. Before these cells infiltrate tissues, however, they contribute to crucial intravascular events in which neutrophil microdomains mediate heterotypic interactions with endothelial cells, red blood cells and/or platelets. In vascular diseases, this can result in exacerbated neutrophil activation, subsequent vascular injury and obstruction of microcirculatory blood flow. This review discusses recent advances in elucidating these neutrophil domains and their associated functions in cell adhesion. Neutrophil recruitment is mediated by sequential interactions with the endothelium, termed rolling, adhesion and extravasation. Evidence points to novel signaling pathways induced during the rolling phase resulting in the transition to leukocyte adhesion, which appear to contribute to chemokine mediated activation. In addition, specific neutrophil microdomains are important for interactions with other hematopoietic cells inducing reductions in microvascular flow and injury. Neutrophils integrate signals received from the endothelium to act as linkers between the vessel wall and a variety of vascular components (i.e. endothelial cells, platelets, red blood cells) in acute and chronic inflammatory conditions to mediate interactions that can result in vascular injury and vasoocclusion.