Infection-stimulated infraosseus inflammation and bone destruction is increased in P-/E-selectin knockout mice

Infections of the dental pulp commonly result in infraosseus inflammation a nd bone destruction. However, the role of phagocytic leucocytes in the path ogenesis of pulpal infections has been uncertain. In this work we used P/E- /- selectin-deficient mice, which lack rolling adhesion of leucocytes to en dothelium and mimic the human syndrome, leucocyte adhesion deficiency II (L AD-II), to test the hypothesis that phagocytic leucocytes protect against p ulpal infection and subsequent periapical infraosseus bone resorption. P/E- /- mice and P/E+/+ wild-type controls were subjected to surgical pulp expos ure, and both groups were infected with a mixture of pulpal pathogens inclu ding Prevotella intermedia, Fusobacterium nucleatum, Peptostreptococcus mic ros and Streptococcus intermedius. Animals were killed after 20 days, and t he extent of infraosseus bone destruction was quantified by histomorphometr y. In two separate experiments, P/E-/- mice had significantly greater bone resorption than P/E+/+ controls. The increased bone destruction correlated with a twofold decrease in polymorphonuclear (PMN) infiltration into periap ical inflammatory tissues of P/E-/- mice. P/E-/- mice had higher tissue lev els of the bone resorptive cytokine, interleukin (IL)-1 alpha. Tissue level s of IL-2, IL-4, IL-10, tumour necrosis factor-alpha (TNF-alpha) and interf eron-gamma (IFN-gamma) were all higher in P/E-/- mice, but the increases we re not statistically significant. Only IL-12 was higher in P/E+/+ mice, pos sibly reflecting a greater number of infiltrating monocytes in wild-type mi ce. These findings demonstrate that phagocytic leucocytes are protective in this model, and suggest that elevated expression of inflammatory cytokines is responsible for the observed bone destruction.