Lactoferrin Interactions with Periodontitis-associated Bacteria - Aspects of Adhesion-counteracting Mechanisms

Abstract: Actinobacillus actinomycetemcomitans, Prevotella intermedia and Prevotella nigrescens are associated with periodontal diseases. Adhesion of these bacteria to host tissue surfaces is a prerequisite for their establishment. The surfaces in the oral cavity are bathed by secretions which emanate from salivary glands and from gingival crevicular area. Lactoferrin is one of the antimicrobial glycoprotein present in several body fluids including saliva and gingival crevicular fluid. The present study describes a novel adhesion-counteracting property of lactoferrin against these periodontal pathogens. The adhesion of A. actinomycetemcomitans, P. intermedia and P. nigrescens to human cells and Matrigel, a reconstituted basement membrane is partly mediated by non-specific ionic interactions. However, these bacteria can specifically interact with human plasma and extracellular matrix proteins. The binding of A. actinomycetemcomitans to laminin is a high affinity interaction. The laminin binding component is a heatmodifiable outer membrane protein. P. intermedia and P. nigrescens also bind fibrinogen, fibronectin, laminin, collagens I and IV A. actinomycetemcomitans binds lactoferrin with two different affinity constants. Lactoferrin specifically binds to the laminin binding protein as well as another outer membrane protein of this bacterium The lactoferrin binding component of P. intermedia and P. nigrescens is also located in the outer membrane and has a molecular weight similar to their laminin binding protein. Lactoferrin competitively inhibits as well as displaces the interaction of A. actinomycetemcomitans to laminin and that of P. intermedia and P. nigrescens to fibrinogen, fibronectin, laminin, collagens I and IV. Presence of lactoferrin also decreases the adhesion of these bacteria to human epithelial cells, fibroblasts and Matrigel. Both specific binding of lactoferrin to these bacteria as well as its non-specific adsorption to human cells and to Matrigel are involved in the inhibitory effect. Lactoferrin in the crevicular fluid may inhibit the adhesion of these bacteria to the periodontal tissues and thereby their establishment. However, lactoferrin can be degraded by some bacteria colonizing the periodontal pocket and this degradation may affect its adhesion-counteracting property.