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Figure 1 | Arthritis Research & Therapy

Figure 1

From: Parietal and intravascular innate mechanisms of vascular inflammation

Figure 1

Checkpoints on leukocyte migration through inflamed vessels and tissues. In the setting of inflamed large arterial vessels, leukocytes adhere to the walls of the vasa vasorum and eventually extravasate through them. After accessing the adventitial layer of large arteries, leukocytes interact with vessel-residing dendritic cells that induce the generation of a follicle-like structure during chronic inflammation (A). In general, circulating leukocytes that approach an inflamed tissue (B) interact with signaling molecules expressed by activated endothelial cells (and platelets), which promote their adhesion to the vessel walls and eventually their migration through endothelial cells and perivascular connective tissue (1). This process mainly occurs at the level of postcapillary venules, where leukocytes are assisted by a first subset of neuron–glial antigen 2-negative/alpha-smooth muscle actin-positive (NG2 α-SMA+) pericytes (2). Both luminal and pericyte-derived signals enhance leukocyte survival and activation. As an example, neutrophils exposed to vascular cell adhesion molecule 1 (VCAM1) live longer: notably VCAM1 is required for the full development of anti-neutrophil cytoplasmic antibody-associated vasculitides glomerulonephritis, while its soluble and endothelial surface expression in rheumatoid arthritis correlates with joint damage and late-stage vascular injury, respectively. After diapedesis, leukocytes move through the interstitial space, mainly following slow and nonlinear routes. Interactions with a second subset of NG2+α-SMA+ arteriolar/capillary pericytes prompt leukocytes to progress faster and more linearly towards target tissues and might be involved in perpetuating vascular inflammation (3). CAM, cell adhesion molecules; vWF, von Willebrand factor.

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