Endothelium-Neutrophil Interactions in ANCA-Associated Diseases

The two salient features of ANCA-associated vasculitis (AAV) are the restricted microvessel localization and the mechanism of inflammatory damage, independent of vascular immune deposits. The nnicrovessel localization of the disease is due to the ANCA antigen accessibility, which is restricted to the membrane of neutrophils engaged in beta 2-integrin-mediated adhesion, while these antigens are cytoplasmic and inaccessible in resting neutrophils. The inflammatory vascular damage is the consequence of maximal proinflammatory responses of neutrophils, which face cumulative stimulations by TNF-alpha, beta 2-integrin engagement, C5a, and ANCA by the Fc gamma RII receptor. This results in the premature intravascular explosive release by adherent neutrophils of all of their available weapons, normally designed to kill IgG-opsonized bacteria after migration in infected tissues.