SALIVARY GLANDS AND SALIVA Number 2 Saliva - the defender of the oral cavity

It is generally accepted that saliva is of paramountimportance for the maintenance of oral health. This isbased on the numerous studies reporting subjective andobjective functional losses that occur in persons wholack the ability to produce adequate volumes of saliva.These include dry mouth feeling (xerostomia), di†cultywith swallowing food, and an increased susceptibilityfor opportunistic infections. The last issue points to anactive protective role of saliva in maintaining oralhealth under normal conditions. The mild climatepresent 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 andanaerobic microorganisms, which together form acomplex and stable ecosystem. For example, the oralmucosal surfaces of the newborn infant are the portalof entry for the majority of pathogenic microorganismsfrom the ﬁrst day of life (Seidel et al, 2001). Salivaplays a key role in maintaining the steady-state of thissystem, as becomes clear when the salivary clearing isblocked, for instance in sedated patients in intensivecare. In the majority of these patients within 2 weeks ashift in the oral microﬂora occurs to Gram-negativespecies, which subsequently spread into the respiratorytract causing pulmonary a‡ictions. This is one exampleof the crucial role played by saliva in the maintenance ofgeneral health, but similar observations can be made inother patients su•ering from an impaired saliva secre-tion. It is recognized for years that saliva contains manycomponents that, in one way or another interact withmicroorganisms, in this way controlling the compositionof the oral microﬂora. In the seventies and eighties ofthe previous century, the main proteins and peptides inhuman saliva have been identiﬁed and characterized (seeFigure 1). Still for a lot of proteins the precise biologicalrole remained elusive as translation of biochemicalproperties to biological functions proved to be di†cultor resulted in erroneous concepts. In the seventies,research focused on elucidation of the role played bysaliva in the protection of dental enamel and identiﬁed alarge number of proteins that in vitro were involved inthe formation of pellicles on hydroxyapatite. Henceforththey were attributed a role in the protection of toothsurfaces. The insight that a lot of so-called saliva-speciﬁcor pellicle-speciﬁc proteins also were present in otherparts of the human body has stimulated further inves-tigation to the biological role in the innate protection ofmucous oral epithelia (Schenkels, Veerman and NieuwAmerongen, 1995b). As a consequence, for some saliv-ary proteins the existing concepts were reﬁned, while forothers a completely di•erent role was found, e.g. asmicrobicidal agents, or as physiological inhibitors ofproteinases.In earlier days the immunoglobulins in saliva havereceived much attention in relation to their speciﬁcprotective function to a single type of microorganism.However, nowadays it has become more clear that, inaddition to this acquired immune system, also an innateimmune system has been secreted into saliva. In the lastyears more light has been shed on the protectivefunctions of the peptides and of the (glyco)proteins ofthe innate immune system, contributing to the ﬁrst lineof oral defence (Frohm Nilsson et al, 1999). In addition,recent research on bacteriostatic (glyco)proteinsrevealed that they have hidden domains possessingmicrobicidic properties that come available after prote-olysis. Although it appears at ﬁrst glance on Figure 1that a redundance to defence mechanisms in saliva ispresent (Rudney, Hickey and Ji, 1999), this has beensuggested only by in vitro studies. In vivo it is clear thatthe inhibiting and killing e•ects are regulated preciselyso that an ecology exists in an equilibrium system in theoral cavity.This mini-review, primarily dealing with the defensivesystems in saliva, will in particular focus on the more