Neutrophils are a type of leukocyte (white blood cell). Neutrophils are first at the site of inflammation. They are involved in the killing of the pathogens and removing “cellular debris”. Normally, neutrophils exist in an inactive form.
Neutrophils are primed by pro-inflammatory cytokines, including tumour necrosis factors-a (TNF-a), interleukin (IL)-18, complement anaphylatoxin C5a (Chemotaxis). Similarly, endotoxins produced by the pathogens can also trigger neutrophil activation.1
In ANCA associated vasculitis, activation of neutrophil is achieved by the migration of the ANCA antigens (i.e. MPO and PR3) to the surface of the cell membrane. The interaction of these antigens via the ANCA Fab’2 and Fc receptors further primes the neutrophils.
This trigger the adhesion of neutrophils via the CD18 integrin, a transmembrane protein that is involved in “cell-cell adhesion”,2 to the intercellular adhesion molecule-1 (ICAM-1) found on the endothelium.3 Neutrophils incubated with anti-CD18 prior to activation has shown have reduced properties of adhesion.4 The neutrophils also release molecules such as oxygen radicals and nitric oxide, which play a role in the damage of the endothelium. 5
Reactive oxygen species, alternative complement activating proteins and proteolytic enzymes causing damage to the endothelium and vascular wall. ANCA activated neutrophils release additional pro-inflammatory cytokines, this recruits more neutrophils amplifying the response. Monocytes are also activated similarly to the neutrophils, which contribute to the vasculitis process, by changing into macrophages. Incubation of ANCA activated neutrophils with endothelial cells have shown to release Von-Willebrand factor, which is an indicator of endothelial stress. Additionally, this increase is observed in patients suffering from Wegener’s granulomatosis.