LPS-neutralizing activities of cathelicidin family of antibacterial polypeptides LL-37 and CAP 11

Abstract

Mammalian myeloid and epithelial cells express several kinds of antibacterial peptides (α-/β-defensins and cathelicidins), which contribute to the innate host defense by killing invaded microorganisms. Recently, we have evaluated the lipopolysaccharide (LPS) -neutralizing activities of cathelicidin peptides human LL-37 and guinea pig CAP 11, using CD 14+ murine macrophage cell line RAW 264.7 and murine endotoxin shock model. LL-37 and CAP 11 inhibited the binding of LPS to RAW 264.7 cells, and suppressed the LPS-induced TNF-α mRNA and protein expression by RAW 264.7 cells. Interestingly, LL-37 and CAP 11 possessed the LPS-binding activities, and they strongly suppressed the interaction of LPS with LPS-binding protein (LBP) that mediates the transport of LPS to CD 14. Moreover, LL 37 and CAP 11 bound to the cell surface CD 14 and inhibited LPS-binding to the cells. Furthermore, in murine endotoxin shock model, LL-37-or CAP 11 -administration inhibited the binding of LPS to CD 14+ cells (peritoneal macrophages) and suppressed the LPS-induced TNF-α expression by these cells. Together these observations indicate that cathelicidin peptides LL 37 and CAP 11 likely exert the protective actions in endotoxin shock by blocking the binding of LPS to CD 14+ cells, thereby suppressing the production of cytokines by these cells via their potent binding activities for LPS and CD 14.