Type 1 diabetes predisposes to enhanced gingival leukocyte margination and macromolecule extravasation in vivo

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Abstract
Sima C, Rhourida K, Van Dyke TE, Gyurko R. Type 1 diabetes predisposes to enhanced gingival leukocyte margination and macromolecule extravasation in vivo. J Periodont Res 2010; 45: 748–756. © 2010 John Wiley & Sons A/S Background and Objective: Diabetes predisposes to periodontal disease. However, the cellular and molecular mechanisms linking the two conditions are not clear. The impact of chronic hyperglycemia on leukocyte margination and macromolecule extravasation was determined in gingival vessels in vivo. Materials and Methods: Gingival intravital microscopy was employed to measure extravasation of fluorescein isothiocyanate (FITC)–dextran in diabetic Akita and healthy wild‐type (WT) mice. Rhodamine 6G and FITC–LY6G were injected for nonspecific and polymorphonuclear‐specific leukocyte labeling, respectively. Surface expression of leukocyte adhesion molecules was determined with flow cytometry and western blotting. Results: Vascular permeability was significantly increased in Akita gingival vessels compared with WT [permeability index (PI): WT, 0.75 ± 0.05; Akita, 1.1 ± 0.03: p < 0.05). Wild‐type gingival vessels reached comparable permeability 2 h after intragingival injection of tumor necrosis factor α (TNFα), used here as positive control (PI, 1.17 ± 0.16). The number of rolling leukocytes was significantly elevated in diabetic gingiva (WT, 25 ± 3.7 cells/min; Akita, 42 ± 8.5 cells/min; p < 0.03). Similar rolling cell counts were obtained in WT after intragingival injection of TNFα (10 ng TNFα, 47 ± 1.3 cells/min; 100 ng TNFα, 57.5 ± 5.85 cells/min). The number of leukocytes firmly attached to the endothelium was similar in WT and Akita mice. Leukocyte cell‐surface expression of P‐selectin glycoprotein ligand‐1 and CD11a was increased in Akita mice, while L‐selectin remained unchanged when compared with WT. Moreover, P‐selectin expression in Akita gingival tissues was elevated compared with that of WT. Conclusion: Chronic hyperglycemia induces a proinflammatory state in the gingival microcirculation characterized by increased vascular permeability, and leukocyte and endothelial cell activation. Leukocyte‐induced microvascular damage, in turn, may contribute to periodontal tissue damage in diabetes.