Intravascular immunity as a key to systemic vasculitis: a work in progress, gaining momentum

Abstract

Vascular inflammation contributes to the defence against invading microbes and to the repair of injured tissues. In most cases it resolves before becoming apparent. Vasculitis comprises heterogeneous clinical entities that are characterized by the persistence of vascular inflammation after it has served its homeostatic function. Most underlying mechanisms have so far remained elusive. Intravascular immunity refers to the surveillance of the vasculature by leucocytes that sense microbial or sterile threats to vessel integrity and initiate protective responses that entail most events that determine the clinical manifestations of vasculitis, such as end-organ ischaemia, neutrophil extracellular traps generation and thrombosis, leucocyte extravasation and degranulation. Understanding how the resolution of vascular inflammation goes awry in patients with systemic vasculitis will facilitate the identification of novel pharmacological targets and bring us a step closer in each patient to the selection of more effective and less toxic treatments.

Keywords: intravascular immunity; pathogenesis; thrombosis; treatment; vasculitis; vessel inflammation.

Fig. 1

Neutrophils degranulate and generate neutrophils extracellular traps (NETs) in response to sterile stimuli. Neutrophils freshly purified from a healthy donor were either left untreated (a) or challenged with purified human P-selectin (b). The expression of pentraxin (PTX)3 (red) and myeloperoxidase (MPO) was analysed by confocal microscopy. (c,d) The generation of NETs upon challenge of adherent neutrophils with the N-formylated formyl-methionyl-leucyl-phenylalanine (fMLP) peptide, which mimics microbial of mitochondrial protein degradation products or interleukin (IL)-8. Hoechst (blue) was used for counterstaining nuclei and extracellular DNA.