Lipopolysaccharide binding protein (LBP) is a member of the PLUNC (Palate Lung Nasal Clone) family of proteins produced in epithelia, including those found in the mouth. Emerging evidence indicates that PLUNC proteins are an important part of the innate immune response to bacterial infection. LBP was for a long time considered to be an acute phase serum protein produced primarily by the liver that catalyzed binding of bacterial lipopolysaccharide (LPS) to Cluster of Differentiation antigen 14 (CD14) leading to Toll-like Receptor 4 (TLR4) dependent induction of inflammatory mediator production. It was thought that LBP served to monomerize LPS present in aggregates or intact bacterial cells and concentrate LPS at the host cell surface for specific recognition by the LPS receptor per se. As knowledge of a monocyte cell surface signaling complex including TLR4 and MD2 (Myeloid Differentiation antigen 2) increased, interest in LBP waned. It is now known that LBP is produced in gingival epithelium and is expressed at a higher level during periodontitis. It is also known to be involved in the recognition of a variety of microbial molecules via multiple recognition pathways. The overall hypothesis to be explored in this proposal is that LBP is an important part of microbial ligand recognition, capable of discriminating minor differences in the diverse ligand structures found in periodontal bacteria. To this end, two Specific Aims are proposed:
Aim 1. Lipopolysaccharide binding protein discrimination of the lipid A fatty acids from oral bacteria and Aim 2. Lipopolysaccharide binding protein recognition of the LPS polysaccharide (LPS-PS) of oral bacteria.
Periodontal (gum) diseases afflict up to 50% of the adult population in the United States with annual costs for the prevention and treatment of periodontal diseases exceeding $14 billion. Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Tannerella forsythia have been implicated as primary bacterial pathogens in periodontal disease. The proposed work explores recognition of specific bacterial cell surface molecules of these organisms by the host innate immune system receptor lipopolysaccharide binding protein (LBP). Recent research suggests an important role for LBP in the transition from gingival health to periodontal disease.