Figure 2. Elements of the innate immune system that detect bacterial lipopolysaccharides (LPS; for review, see Triantafilou and Triantafilou, 2002; Weiss, 2003). LBP and BPI are similar lipophilic molecules that act as antagonists in the immune response to Gram-negative bacteria. (1) LBP binds to LPS and ferries it to a cell-surface receptor complex including CD14 and Toll-like receptors (TLRs). This stimulates the receiving cell to mount an immune response. (2) BPI acts as an antagonist to LBP, removing LPS from LBP interactions. (3) BPI also facilitates the transfer of LPS to phagocytic cells, where it is degraded. At least seven PLUNC proteins are predicted in humans. They have structural similarities to BPI and may act along similar pathways. Most interactions are speculative, as shown by dotted lines. (4) Like LBP, long PLUNC proteins could bind microbial molecules and present them to epithelial or immune cells. (5) Short PLUNC proteins from this multi-gene family could antagonize these signaling pathways, sequestering microbial molecules from immune detection. (6) Finally, like BPI, long PLUNC proteins could accelerate clearance of microbial molecules from the epithelial environment.