Evidence for a self-enforcing inflammation in neutrophil-mediated chronic diseases

Abstract

In summary, this thesis provides evidence for the self-sustaining role of neutrophils in the inflammatory state in the pathogenesis of COPD and CD. In active disease, neutrophils release proteolytic enzymes that breakdown collagen. One of the collagen fragments can be neutrophilic chemoattractant N-ac-PGP, which leads to enhanced neutrophil inflammation and further inflammation. In COPD, cigarette smoking initiates a vicious circle of events leading to collagen breakdown, PGP generation and PGP-induced neutrophilic transmigration (fig. 1). This PGP generation can also play a significant role in the pathogenesis of CD, since neutrophils from CD patients generate higher amounts of PGP from whole collagen under basal conditions than neutrophils from healthy controls. It was proposed that intestinal damage initiates a vicious circle of events leading to collagen breakdown, PGP generation and PGP-induced neutrophilic transmigration (fig. 2). Since N-ac-PGP likely plays a significant role in both chronic diseases, N-ac-PGP is a very interesting drug target. Medication such as CXCR2 antagonists or MMP and PE inhibitors could be provided to tackle the sustained neutrophilic inflammation.