Saliva – the defender of the oral cavity

Abstract

It is generally accepted that saliva is of paramount importance for the maintenance of oral health. This is based on the numerous studies reporting subjective and objective functional losses that occur in persons who lack the ability to produce adequate volumes of saliva. These include dry mouth feeling (xerostomia), difficulty with swallowing food, and an increased susceptibility for opportunistic infections. The last issue points to an active protective role of saliva in maintaining oral health under normal conditions. The mild climate present in the oral cavity, i.e. an elevated temperature, a high humidity and regular supply of foodstuffs, fosters the growth of a myriad of different aerobic and anaerobic microorganisms, which together form a complex and stable ecosystem. For example, the oral mucosal surfaces of the newborn infant are the portal of entry for the majority of pathogenic microorganisms from the first day of life (92). Saliva plays a key role in maintaining the steady-state of this system, as becomes clear when the salivary clearing is blocked, for instance in sedated patients in intensive care. In the majority of these patients within 2 weeks a shift in the oral microflora occurs to Gram-negative species, which subsequently spread into the respiratory tract causing pulmonary afflictions. This is one example of the crucial role played by saliva in the maintenance of general health, but similar observations can be made in other patients suffering from an impaired saliva secretion. It is recognized for years that saliva contains many components that, in one way or another interact with microorganisms, in this way controlling the composition of the oral microflora. In the seventies and eighties of the previous century, the main proteins and peptides in human saliva have been identified and characterized (see Figure 1). Still for a lot of proteins the precise biological role remained elusive as translation of biochemical properties to biological functions proved to be difficult or resulted in erroneous concepts. In the seventies, research focused on elucidation of the role played by saliva in the protection of dental enamel and identified a large number of proteins that in vitro were involved in the formation of pellicles on hydroxyapatite. Henceforth they were attributed a role in the protection of tooth surfaces. The insight that a lot of so-called saliva-specific or pellicle-specific proteins also were present in other parts of the human body has stimulated further investigation to the biological role in the innate protection of mucous oral epithelia (90). As a consequence, for some salivary proteins the existing concepts were refined, while for others a completely different role was found, e.g. as microbicidal agents, or as physiological inhibitors of proteinases. Schematic presentation of the main functions of saliva in relation to its constituents In earlier days the immunoglobulins in saliva have received much attention in relation to their specific protective function to a single type of microorganism. However, nowadays it has become more clear that, in addition to this acquired immune system, also an innate immune system has been secreted into saliva. In the last years more light has been shed on the protective functions of the peptides and of the (glyco)proteins of the innate immune system, contributing to the first line of oral defence (27). In addition, recent research on bacteriostatic (glyco)proteins revealed that they have hidden domains possessing microbicidic properties that come available after proteolysis. Although it appears at first glance on Figure 1 that a redundance to defence mechanisms in saliva is present (85), this has been suggested only by in vitro studies. In vivo it is clear that the inhibiting and killing effects are regulated precisely so that an ecology exists in an equilibrium system in the oral cavity. This mini-review, primarily dealing with the defensive systems in saliva, will in particular focus on the more recently obtained data, aiming to (re)interpret earlier observations on the basis of our present knowledge. In this respect it is intended to give an update of the current knowledge and insights in the protective role of salivary components. The earliest studies on salivary mucins concluded that these glycoproteins occurred as a single high molecular weight species containing blood group activity (68). Later studies, using more stringent isolation and analytical techniques demonstrated that human saliva contains two genetically distinct mucin types, designated MG1 and MG2 (56; 76; 100), originating from the MUC5B and MUC7 gene, respectively (12; 22). MUC7 (MG2) has been found to exist as at least two glycoforms, MG2a and MG2b, respectively (8). In addition, genetic polymorphism has been shown for MUC7, which is associated with asthma (50). Salivary MUC5B (MG1), which displays blood group activity, exists in at least three different glycoforms, differi