Saliva – the defender of the oral cavity

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), diculty 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 foodstu€s, fosters the growth of a myriad of di€erent 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 ®rst day of life (Seidel et al, 2001). 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 micro ̄ora occurs to Gram-negative species, which subsequently spread into the respiratory tract causing pulmonary a‚ictions. 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 su€ering 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 micro ̄ora. In the seventies and eighties of the previous century, the main proteins and peptides in human saliva have been identi®ed 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 dicult 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 identi®ed 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-speci®c or pellicle-speci®c 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 (Schenkels, Veerman and Nieuw Amerongen, 1995b). As a consequence, for some salivary proteins the existing concepts were re®ned, while for others a completely di€erent role was found, e.g. as microbicidal agents, or as physiological inhibitors of proteinases. In earlier days the immunoglobulins in saliva have received much attention in relation to their speci®c 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 ®rst line of oral defence (Frohm Nilsson et al, 1999). 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 ®rst glance on Figure 1 that a redundance to defence mechanisms in saliva is present (Rudney, Hickey and Ji, 1999), this has been suggested only by in vitro studies. In vivo it is clear that the inhibiting and killing e€ects 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 Correspondence: Prof Dr AV Nieuw Amerongen, Department of Dental Basic Sciences, Section Oral Biochemistry, ACTA, Medical Faculty, Vrije Universiteit, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. Tel.: +31 20 444 8675, Fax: 0031 20 444.8685, E-mail: a.van_nieuw_amerongen.obc.acta@med.vu.nl Oral Diseases (2002) 8, 12±22 Ó 2002 Munksgaard All rights reserved 1354-523X/01