Figure 1.

Recognition of endotoxin (lipopolysaccharide [LPS]) on the surface of phagocytes and mechanism of polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) treatment. LPS is opsonized by LPS-binding protein (LBP), and LPS-LBP complex is recognized by CD14, on the monocyte and macrophage surface. LPS-LBP-CD14 ternary complex activates TLR4, which in turn signals through My88 and interleukin (IL)-1 receptor-associated kinase (IRAK). Signaling pathways activate nuclear factor kappa B (NF-kB), which induces the production of proinflammatory cytokines and nitric oxide (NO). PMX-DHP directly adsorbs endotoxin and reduces circulating level of endotoxin. In addition, PMX-DHP adsorbs monocyte and anandamide. As a result, inflammatory cytokines and NO decrease. TLR4: Toll-like receptor 4; MD2: myeloid differentiation 2; MyD88: myeloid differentiation factor 88; TNF: tumor necrosis factor.