FIG. 10.

TLR-4 mediates HMGB1-induced reactive oxygen species (ROS) production. The integral membrane of the phagocyte consists of two subunits: p22phox and gp91phox, which, respectively, produce the smaller and larger chain of the cytochrome-b558. Two cytosolic subunits (p67phox and p47phox), a p40phox accessory protein, and an Rac-GTP binding protein then translocate to the cell membrane upon cell activation to form the NADPH oxidase complex, which generates a respiratory burst. Hemorrhagic shock/resuscitation-induced HMGB1 release. HMGB1 increases neutrophil NADPH oxidase activation and subsequent ROS production by TLR-4-MyD88-IRAK4 signaling. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article at www.liebertonline.com/ars).