TIE1 and Sepsis: In the context of sepsis, stimuli of inflammatory cytokines, coagulants, or VEGF allow secretion of Ang2 from WPB.162,362 Ang2 itself serve as a rapidly acting regulator of the endothelium through an autocrine loop mechanism.363 In the presence of LPS or infection signals, ectodomain cleavage of Tie1 block Tie2 phosphorylation and contribute to loss of agonist property of Ang2 as well as weakened Ang1 activity.158,161 This suggest the indispensable role of Tie1 in Tie2 signaling.