Lactoferrin Knockout Mice Exhibit Greater Susceptibility to Localized Aggressive Periodontitis

Objectives: Lactoferrin (Lf) is an iron-binding 80-kDa glycoprotein found in milk, mucosal secretion and neutrophil secondary granules with antimicrobial and immunomodulatory activities. To understand the significance of Lf in periodontal disease, susceptibility of wild type and Lf knockout (Lf^-/-) mice were compared in an experimental periodontal disease model. Different outcomes in the two groups of animals could be a direct result of the absence of Lf in the knockout mice establishing the significance of Lf in periodontal infection. Methods: Periodontal disease was established through an oral feeding of 100μl of Aa (1x10⁹) with 2% carboxymethylcellulose to facilitate the retention of the bacterial cells in the oral cavity. A second direct injection of 10μl Aa into the palatal gingival tissue of the second molar was administered to ensure establishment of periodontal disease in 100% of the animals. The effectiveness of infection was confirmed by the detection of Aa in periodontal tissues by PCR. Additionally, the sera of mice were tested for antibodies against Aa using ELISA. The presence of disease was ascertained by measuring alveolar bone loss after 60 days of Aa infection. Results: Aa-fed mice showed higher titers compared to sham infected mice and more importantly, antibody titers (IgG) were higher for Lf^-/- mice when compared to wild-type mice. The wild type Aa infected group showed significantly higher bone loss when compared to the uninfected controls. Similarly, The  Aa infected Lf^-/- mice showed significantly higher bone loss when compared to its control and Aa infected wild type control (p<0.01). Conclusion: The results provide evidence that Lf^-/- mice are more susceptible to Aa-induced periodontal infection as evidenced by the significantly higher bone loss when compared to the control animals.