Chronic hyperglycemia predisposes to exaggerated inflammatory response and leukocyte dysfunction in Akita mice

Robert Gyurko, Camille Colares Siqueira Nogueira, Nathaniel Caldon, Li Gao, Alpdogan Kantarci, Thomas E. Van Dyke

Research output: Contribution to journalArticle

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Abstract

The role of polymorphonuclear neutrophils (PMN) in mediating diabetic tissue damage to the periodontium was investigated in a novel model of chronic hyperglycemic, the Akita mouse. Induction of acute peritoneal inflammation in wild-type (WT) and Akita mice resulted in exaggerated IL-6 response in Akita mice (2.9-fold increase over WT values) and a markedly increased chemokine response (KC, 2.6-fold; MCP-I, 2.6-fold; and MIP-1α:, 4.4-fold increase over WT values). Chemotaxis to both fMLP and WKYMVm was significantly reduced in isolated Akita PMN compared with WT PMN as measured in a Boyden chamber. Superoxide release in contrast was significantly increased in Akita PMN as measured with cytochrome c reduction. Bone marrow-derived Akita PMN showed partial translocation of p47phox to the cell membrane without external stimulation, suggesting premature assembly of the superoxide-producing NADPH oxidase in hyperglycemia. In vivo studies revealed that ligature-induced periodontal bone loss is significantly greater in Akita mice compared with WT. Moreover, intravital microscopy of gingival vessels showed that leukocyte rolling and attachment to the vascular endothelium is enhanced in periodontal vessels of Akita mice. These results indicate that chronic hyperglycemia predisposes to exaggerated inflammatory response and primes leukocytes for marginalization and superoxide production but not for transmigration. Thus, leukocyte defects in hyperglycemia may contribute to periodontal tissue damage by impairing the innate immune response to periodontal pathogens as well as by increasing free radical load in the gingival microvasculature.

Original languageEnglish (US)
Pages (from-to)7250-7256
Number of pages7
JournalJournal of Immunology
Volume177
Issue number10
DOIs
StatePublished - Nov 15 2006
Externally publishedYes

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Hyperglycemia
Neutrophils
Leukocytes
Superoxides
Leukocyte Rolling
Alveolar Bone Loss
Periodontium
Obese Mice
NADPH Oxidase
Vascular Endothelium
Chemotaxis
Microvessels
Cytochromes c
Chemokines
Innate Immunity
Free Radicals
Ligation
Interleukin-6
Bone Marrow
Cell Membrane

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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Chronic hyperglycemia predisposes to exaggerated inflammatory response and leukocyte dysfunction in Akita mice. / Gyurko, Robert; Siqueira Nogueira, Camille Colares; Caldon, Nathaniel; Gao, Li; Kantarci, Alpdogan; Van Dyke, Thomas E.

In: Journal of Immunology, Vol. 177, No. 10, 15.11.2006, p. 7250-7256.

Research output: Contribution to journalArticle

Gyurko, Robert ; Siqueira Nogueira, Camille Colares ; Caldon, Nathaniel ; Gao, Li ; Kantarci, Alpdogan ; Van Dyke, Thomas E. / Chronic hyperglycemia predisposes to exaggerated inflammatory response and leukocyte dysfunction in Akita mice. In: Journal of Immunology. 2006 ; Vol. 177, No. 10. pp. 7250-7256.
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