Figure 3

Model of PMN NADPH oxidase-derived oxidant signaling in mediating the TLR4-TLR2 cross-talk in ECs. LPS stimulation induces NAD(P)H oxidase activation and production of ROS in PMN as well as the initiation of MyD88-dependent NF-κB signaling in ECs and the consequent expression of TLR2 and ICAM-1. Adhesion of PMN to ECs is mediated by 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-κB signaling and TLR2 expression (+), which results 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 NAD(P)H oxidase-mediated TLR4-TLR2 cross-talk activates a positive feedback signal leading to sustained and amplified endothelial activation in response to invading pathogens. (The figure is adapted from [68] and used with permission from the Journal of Clinical Investigation.)