Vascular monitoring of the arterial endothelium by patrolling monocytes

KONRAD BUSCHER, AMADO QUINTAR, SARA MCARDLE, ZBIGNIEW MIKULSKI, KLAUS LEY

Congreso; 42nd La Jolla Immunology Conference; 2016

The Ly6Clow subset of murine monocytes is uniquely capable of monitoring the vessels of the microcirculation in order to maintain homeostasis. Due to technical challenges of imaging pulsating large arteries, leukocyte-endothelial interactions have rarely been observed. Here, we established a two-photon intravital microscopy setup that allows long-term stable 2D and 3D imaging of the unrestrained carotid artery using triggered acquisition and post-processing. We observe a basal population of patrolling monocytes that continuously meander along arterial endothelium at a velocity of 30 µm/s, with and against the flow, despite high shear conditions. TLR-7 agonists and hyperlipidemia upregulate patrolling 9-fold in an LFA-1 and a4-integrin dependent, and CX3CR1-independent manner. In atherosclerotic plaque-prone arteries using ApoE-/- mice, monocytes are readily captured onto the endothelial layer from free flow. Here, patrolling is 22-fold increased, alternates with rolling behavior and localizes to definedendothelial areas. These data introduce the concept of arterial monocyte Patrolling, lay out molecular and microkinetic differences to the Microcirculation, and suggest relevance in inflammatory disorders of large arteries