BPI-Like proteins in Oral and Airway Epithelia

Lipopolysaccharide-binding protein (LBP) and bactericidal/permeability-increasing protein (BPI) are closely related endotoxin-binding proteins that function in a co-ordinated manner to facilitate an integrated host response to invading Gram-negative bacteria. Differences in the structure and function of BPI and LBP, as well as differences in their mobilization, permit highly sensitive pro-inflammatory responses to small numbers of bacteria at the onset of bacterial invasion and, later, efficient elimination of viable bacteria and their remnants and of endotoxin-driven inflammation. Introduction Multicellular organisms are continuously challenged by the intrusion of micro-organisms that abound in the surrounding environment. When this includes microbes that can proliferate rapidly outside host cells, even the incursion of a few organisms can soon pose a risk if microbial multiplication proceeds unabated. To combat this problem, multicellular organisms have evolved highly efficient machinery to selectively recognize invading micro-organisms, and to couple microbial recognition to the mobilization of host defence systems permitting elimination of viable microbes and their remnants before appreciable proliferation and dissemination ensues. For defence against many invading Gram-negative bacteria (GNB), the recognition of endotoxins, unique surface glycolipids of GNB, has provided a key strategy linked to the induction of inflammation, targeting of GNB for elimination and clearance of the endotoxin itself (Figure 1). Endotoxins of GNB Endotoxins [lipopolysaccharides (LPSs) and lipo-oligosaccharides (LOSs)] are present only in GNB, where they occupy much of the outer leaflet of the unique outer membrane (OM) of GNB [1] (Figure 2). Endotoxins are composed of a conserved lipid A region, a β1→6-linked disaccharide of N-acetylglucosamine substituted with non-hydroxylated