title: Lack of p47(phox) in Akita Diabetic Mice Is Associated with Interstitial Pneumonia, Fibrosis, and Oral Inflammation.
abstract: Excess reactive oxygen species production is central to the development of diabetic complications. The contribution of leukocyte reactive oxygen species produced by the NADPH oxidase to altered inflammatory responses associated with uncontrolled hyperglycemia is poorly understood. To get insight into the role of phagocytic superoxide in the onset of diabetic complications, we used a model of periodontitis in mice with chronic hyperglycemia and lack of leukocyte p47(phox) (Akita/Ncf1) bred from C57BL/6-Ins2(Akita)/J (Akita) and neutrophil cytosolic factor 1 knockout (Ncf1) mice. Akita/Nfc1 mice showed progressive cachexia starting at early age and increased mortality by six months. Their lungs developed infiltrative interstitial lesions that obliterated air spaces as early as 12 weeks when fungal colonization of lungs also was observed. Neutrophils of Akita/Ncf1 mice had normal degranulation and phagocytic efficiency when compared with wild-type mice. Although Akita/Ncf1 mice had increased prevalence of oral infections and more severe periodontitis compared with wild-type mice, bone loss was only marginally higher compared with Akita and Ncf1 null mice. Altogether these results indicate that lack of leukocyte superoxide production in mice with chronic hyperglycemia results in interstitial pneumonia and increased susceptibility to infections.
authors.affiliation: Department of Periodontology and Oral Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, Massachusetts.
authors.forename: Mai F
authors.initials: MF
authors.lastname: Zamakhchari
authors.affiliation: Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, Massachusetts; Department of Oral Medicine, Infection, Immunity, Harvard School of Dental Medicine, Boston, Massachusetts.
authors.forename: Corneliu
authors.initials: C
authors.lastname: Sima
authors.affiliation: Department of Periodontology and Oral Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, Massachusetts.
authors.forename: Kishore
authors.initials: K
authors.lastname: Sama
authors.affiliation: The Matrix Dynamics Group, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Noah
authors.initials: N
authors.lastname: Fine
authors.affiliation: The Matrix Dynamics Group, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Glogauer
authors.affiliation: Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, Massachusetts; Department of Oral Medicine, Infection, Immunity, Harvard School of Dental Medicine, Boston, Massachusetts.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Van Dyke
authors.affiliation: Department of Periodontology and Oral Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, Massachusetts; Department of Periodontology, Tufts University School of Dental Medicine, Boston, Massachusetts. Electronic address: robert.gyurko@tufts.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Gyurko
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D005355:Fibrosis; D006943:Hyperglycemia / Q000150:complications / Q000276:immunology / Q000473:pathology*; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009055:Mouth / Q000473:pathology; D009154:Mutation; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D010518:Periodontitis / Q000150:complications / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: C561967:Ins2 protein, mouse; D007328:Insulin; D017382:Reactive Oxygen Species; D013481:Superoxides; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1