HOST DEFENSE FACTORS IN ORAL ECOLOGY

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Saliva contains a number of proteins which display antinicrobial activity in vitro. These include lysozyme (Lz), lactoferrin (Lf), salivary peroxidase (Spx), secretory immunoglobulin A (sIgA), the mucin glycoproteins (MG1 and MG2), and others less well known. Strains of streptococcal species vary greatly in susceptibility to effects of these proteins, and their role in oral ecology is not yet clear. Interpretation of previous studies is complicated by recent research which suggests that antimicrobial proteins may interact in a recent research which suggests that antimicrobial proteins may interact in a common system for host defense. Interactions may be synergistic or antagonistic, and appear to vary with concentrations of proteins involved. Those findings have direct implications for investigations of defense factor effects in vivo. Previous clinical studies have focused on single proteins, and results have been inconclusive. One reason might be interaction between defense system components. A multiple protein approach thus may be needed. An important first step is description of the ways in which host factor concentrations may vary together in the population at large. Ongoing research by the principal investigator employs multivariate statistical methods to address this problem in a large student sample. Those methods allow identification of groups of subjects with similar concentration profiles for Lz, Lf, Spx, sIgA, and (in the near future) MG1 and MG2. Such groups provide a basis for comparison of persons likely to display distinct and different patterns of interaction. This project will apply that approach in the context of two working hypotheses. The first is that host defense factors may exert selective effects on the composition of dental plaque. The second is that host defense factors may contribute to regulation of the metabolic activity of plaque. The effect of differences in host factor composition on these variables will be investigated by comparing subjects belonging to groups with extremely high or low values for one or more antimicrobial proteins. Restriction endonuclease chromosomal DNA fingerprinting and other molecular techniques will be used to characterize and compare streptococcal floras between subjects (see Microbiology component, Project A1). Microelectrode methods will be used to compare acid production curves between subject plaques (see Microbiology component, Project A8). Information obtained will be used to re-cast working hypotheses in terms of specific research questions. Designs devised to address those questions should contribute greatly to understanding of the role of host defense factors as determinants of interperson differences in oral ecology.