Complement mediators in ischemia–reperfusion injury

C5a, A Complement Activation Product, Is a Useful Marker in Predicting the Severity of Necrotizing Enterocolitis

“…During complement activation by one of these pathways, complement component C5 is proteolytically cleaved, resulting in C5a anaphylatoxin that is a potent inflammatory peptide triggering a variety of proinflammatory events which lead to local and systemic inflammation (Köhl 2001). Additionally, it has been reported that C5a is not only produced systemically but also produced locally in different tissues such as the liver, lung and intestine, as a response to injury and is released in to the blood stream (Arumugam et al 2006). Some studies have also demonstrated that C5a, produced by different tissues such as the intestine, stimulates the release of several cytokines such as IL-6, IL-1β, TNF-α, inflammatory mediators (e.g., CRP) and chemokines to the blood stream (Fleming et al 2003;Arumugam et al 2006).…”

“…Ischemia-reperfusion (I/R) injury was found to be an important factor in triggering complement activation in experimental studies (Arumugam et al 2006). Moreover, abnormal colonization, possibly a source of microbial cell wall products, in the intestinal tract of premature neonates may contribute to the onset of NEC (Lin et al 2008;Thompson and Bizzarro 2008;Schnabl et al 2008), and may trigger complement activation by three pathways resulting in C5a production (Arumugam et al 2006). Therefore, involvement of the complement system might have an important role in the development of NEC.…”

“…Additionally, it has been reported that C5a is not only produced systemically but also produced locally in different tissues such as the liver, lung and intestine, as a response to injury and is released in to the blood stream (Arumugam et al 2006). Some studies have also demonstrated that C5a, produced by different tissues such as the intestine, stimulates the release of several cytokines such as IL-6, IL-1β, TNF-α, inflammatory mediators (e.g., CRP) and chemokines to the blood stream (Fleming et al 2003;Arumugam et al 2006).…”

“…The complement cascade, involving many different components, can be activated by any one of three pathways, the antibody-dependent classic pathway, the antibody-independent alternative pathway or the mannose-binding lectin/ mannose-binding lectin-associated serine protease pathway (MBL/MASP) (Kirschfink 1997;Arumugam et al 2004Arumugam et al , 2006. The classical pathway is typically initiated when IgM or IgG antigen/antibody complexes bind to the first component of the complement system, C1.…”

“…The alternative pathway is triggered by microbial cell surfaces and a variety of complex polysaccharides. The MBL/MASP pathway is initiated through the binding of MBL protein to mannose or glucosamine residues on bacterial cell walls (Arumugam et al 2004(Arumugam et al , 2006. During complement activation by one of these pathways, complement component C5 is proteolytically cleaved, resulting in C5a anaphylatoxin that is a potent inflammatory peptide triggering a variety of proinflammatory events which lead to local and systemic inflammation (Köhl 2001).…”