title: Role of angiopoietin-2 in infection - A double-edged sword?
abstract: The endothelial angiopoietin (Angpt)/Tie2 ligand receptor system maintains vascular quiescence and modulates the response to injury. Angpt-1 is considered the natural Tie2 agonist and receptor ligation leads to its phosphorylation inducing various protective downstream pathways. The natural antagonist - Angpt-2 - appears to inhibit these protective effects. In sepsis, the balance between both ligands is shifted in favor for Angpt-2 and the vasculature is highly dysfunctional, activated and leaky. Circulating levels of Angpt-2 strongly predict mortality in septic patients. Consistently, experimental strategies that target Angpt-2 (e.g. antibody, RNAi, etc.) can protect the vascular barrier and improve survival. However, in vitro is has also been shown that Angpt-2 can act as a dose-dependent Tie2 agonist/antagonist. Based on this, people have wondered if Angpt-2 is per se injurious or if it might have protective effects dependent on the scenario. A recent paper by Safioleas and colleagues showed survival benefits after a therapeutic injection of recombinant Angpt-2 in experimental pyelonephritis. Here, we discuss their counter-intuitive but interesting findings and put them into a global context with respect to the existent literature in the angiopoietin/Tie2 sepsis field.
authors.affiliation: Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Thamm
authors.affiliation: Division of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany. Electronic address: david.sascha@mh-hannover.de.
authors.forename: Sascha
authors.initials: S
authors.lastname: David
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism; D042702:Angiopoietin-2 / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D011704:Pyelonephritis / Q000188:drug therapy / Q000378:metabolism*; D042787:Receptor, TIE-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism*
chemical_list: C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042787:Receptor, TIE-2
keywords: Angiopoietin-2; Endothelium; Infection; Sepsis