Association of Toll-Like Receptor Signaling and Reactive Oxygen Species: A Potential Therapeutic Target for Posttrauma Acute Lung Injury

Figure 4

Role of PMN NADPH oxidase-derived oxidant signaling in mediating the TLR4-TLR2 cross talk in ECs. LPS stimulation induces NADPH oxidase activation and production of reactive oxygen species (ROS) in PMN as well as the initiation of MyD88-dependent NF-$\kappa$B signaling in ECs and the consequent expression of TLR2 and ICAM-1. Adhesion of PMN to ECs is mediated by the binding of constitutive ICAM-1 to CD18 integrin and provides the appropriate coupling required for PMN to transmit oxidant signals to ECs. The oxidants augment NF-$\kappa$B signaling and TLR2 expression (+), which result in the augmented response of the cell to PGN, thereby amplifying ICAM-1 expression (circled +) and promoting stable adhesion of PMN to ECs and increased PMN migration. Thus, the PMN NADPH oxidase-mediated TLR4-TLR2 cross talk activates a positive feedback signal leading to sustained and amplified endothelial activation in response to invading pathogens.