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

N. Kawashima, Richard Niederman, R. O. Hynes, M. Ullmann-Cullere, P. Stashenko

Research output: Contribution to journalArticle

Abstract

Infections of the dental pulp commonly result in infraosseus inflammation and bone destruction. However, the role of phagocytic leucocytes in the pathogenesis of pulpal infections has been uncertain. In this work we used P/E(-/-) selectin-deficient mice, which lack rolling adhesion of leucocytes to endothelium and mimic the human syndrome, leucocyte adhesion deficiency II (LAD-II), to test the hypothesis that phagocytic leucocytes protect against pulpal infection and subsequent periapical infraosseus bone resorption. P/E(-/-) mice and P/E(+/+) wild-type controls were subjected to surgical pulp exposure, and both groups were infected with a mixture of pulpal pathogens including Prevotella intermedia, Fusobacterium nucleatum, Peptostreptococcus micros and Streptococcus intermedius. Animals were killed after 20 days, and the extent of infraosseus bone destruction was quantified by histomorphometry. 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 periapical inflammatory tissues of P/E(-/-) mice. P/E(-/-) mice had higher tissue levels of the bone resorptive cytokine, interleukin (IL)-1α. Tissue levels of IL-2, IL-4, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were all higher in P/E(-/-) mice, but the increases were not statistically significant. Only IL-12 was higher in P/E(+/+) mice, possibly reflecting a greater number of infiltrating monocytes in wild-type mice. 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.

Original languageEnglish (US)
Pages (from-to)117-123
Number of pages7
JournalImmunology
Volume97
Issue number1
DOIs
StatePublished - 1999

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Osteitis
P-Selectin
E-Selectin
Knockout Mice
Infection
Bone and Bones
Leukocytes
Bone Resorption
Leukocyte-Adhesion Deficiency Syndrome
Streptococcus intermedius
Periapical Tissue
Prevotella intermedia
Leukocyte Rolling
Fusobacterium nucleatum
Cytokines
Peptostreptococcus
Dental Pulp
Interleukin-12
Interleukin-1
Interleukin-4

ASJC Scopus subject areas

  • Immunology

Cite this

Infection-stimulated infraosseus inflammation and bone destruction is increased in P-/E-selectin knockout mice. / Kawashima, N.; Niederman, Richard; Hynes, R. O.; Ullmann-Cullere, M.; Stashenko, P.

In: Immunology, Vol. 97, No. 1, 1999, p. 117-123.

Research output: Contribution to journalArticle

Kawashima, N. ; Niederman, Richard ; Hynes, R. O. ; Ullmann-Cullere, M. ; Stashenko, P. / Infection-stimulated infraosseus inflammation and bone destruction is increased in P-/E-selectin knockout mice. In: Immunology. 1999 ; Vol. 97, No. 1. pp. 117-123.
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