Involvement of platelet-activating factor in cytokine production and neutrophil activation after hepatic ischemia-reperfusion

Abstract

Although platelet-activating factor (PAF) is impli-the basis of hepatic IR injury. Recent studies in this cated as an important mediator in the pathogenesis of field have focused on the involvement of inflammatory hepatic ischemia-reperfusion (IR) injury, the precise cytokines and neutrophils. [1][2][3][4][5][6] Tumor necrosis factor a mechanism of its action has not been studied. We exam-(TNF-a) is reported to have a pivotal role in the cytoined the hypothesis that PAF may influence neutrophils kine cascade and in the activation of neutrophils, 7,8 and by promoting the production of tumor necrosis factor a it has been suggested to be involved in hepatic IR in-(TNF-a) and cytokine-induced neutrophil chemoattrac-jury. 1 In association with cytokine production, much tant (CINC), a member of the interleukin-8 (IL-8) family, attention has been devoted to the fact that IR of the and may be associated with liver and lung injury during liver, 1 gastrointestinal tract, 9 or lower torso 10 induces the early phase of reperfusion after total hepatic isch-lung injury as distant organ damage. Interleukin-8 (ILemia. Rats pretreated with a specific PAF receptor an-8) 11,12 is an inflammatory cytokine produced by the tagonist exhibited suppression of the increase in plasma stimulation of many types of cells, including mono-TNF-a and CINC levels, as well as the priming of periphcytes, macrophages, and endothelial cells, along with eral neutrophils for superoxide production after reperfusion when compared with animals pretreated with TNF-a and interleukin-1. This cytokine acts as a neuphysiological saline. These effects resulted in a reduc-trophil chemoattractant/activator and has been implition of plasma liver enzymes and of hepatic and pulmo-cated in reperfusion injury. 13 Although a rat equivalent nary neutrophil sequestration, as well as an increased of human IL-8 has not yet been identified, rat cytokinesurvival rate. There was a strong correlation between induced neutrophil chemoattractant (CINC) 14-16 is bethe time course of CINC release and hepatic or pulmo-lieved to be a counterpart of human melanoma growth nary neutrophil sequestration. We concluded that PAF stimulatory activity/growth-related oncogene (gro), activates neutrophils, either directly or by promoting which is classed as a member of the IL-8 family on the the production of TNF-a and CINC, and is involved in basis of its primary structure. However, no definitive evidence is available on the involvement of IL-8/CINC in liver and lung injury following hepatic IR. Hepatic ischemia-reperfusion (IR) injury is an ineviPlatelet-activating factor (PAF) has multiple effects table problem in liver transplantation, extensive hepa-on neutrophils including the promotion of chemotaxis tectomy, and hypovolemic shock. The most important and superoxide production, and priming. 17,18 PAF also consequence is multiple organ failure with a high mor-induces the production of cytokines such as TNF-a, tality rate, so there has been considerable interest in interleukin-6, and IL-8 b...

ZnPP reduces autophagy and induces apoptosis, thus aggravating liver ischemia/reperfusion injury in vitro

“…Previous studies have identified a number of key factors associated with liver IR injury, such as Toll-like receptor (TLR), HO, leukocyte cascades and oxygen-free radicals (OFRs) (17,18). Understanding the mechanism of IR injury is crucial to reducing liver injury during liver surgery.…”

Protection from ischemic liver injury by activation of A2Aadenosine receptors during reperfusion: inhibition of chemokine induction

“…Severe hepatic I/R injury causes not only liver failure but damage to other organs (14). Inflammatory events that occur during reperfusion lead to disruption of the integrity of the vascular endothelium and sinusoids, platelet aggregation, immunocyte activation (monocytes/macrophages, Kupffer cells, neutrophils), chemokine and cytokine secretion, and complement activation (32,45).…”

Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice

“…2 Experimental reperfusion injury involves a cascade of events initiated by reactive oxygen intermediates (ROI) and ultimately resulting in graft invasion by polymorphonuclear cells and lymphocytes. Among the intermediate steps of this proinflammatory cascade, membrane derived compounds such as plateletactivating factor 3,4 ; cytokines like tumor necrosis factor (TNF), epithelial-activating neutrophil protein 78, and macrophage inflammatory protein 2 [5][6][7][8] ; and adhesion molecules including the CD18 family, intracellular adhesion molecule 1, and selectins [9][10][11][12] play a pivotal role in the recruitment and activation of neutrophils, the final mediators of injury. 9,13,14 Most of these events are thought to be mainly dependent on Kupffer cell activation.…”