title: Type 1 diabetes predisposes to enhanced gingival leukocyte margination and macromolecule extravasation in vivo.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Sima
authors.forename: K
authors.initials: K
authors.lastname: Rhourida
authors.forename: T E
authors.initials: TE
authors.lastname: Van Dyke
authors.forename: R
authors.initials: R
authors.lastname: Gyurko
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000502:physiology; D002448:Cell Adhesion; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular; D005260:Female; D005881:Gingiva / Q000098:blood supply* / Q000473:pathology; D005891:Gingivitis / Q000503:physiopathology; D006943:Hyperglycemia / Q000503:physiopathology*; D019041:L-Selectin / Q000096:biosynthesis; D036904:Leukocyte Rolling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D055806:Microvessels / Q000503:physiopathology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D019007:P-Selectin / Q000096:biosynthesis
chemical_list: D019007:P-Selectin; D019041:L-Selectin