Involvement of semicarbazide-sensitive amine oxidase-mediated deamination in lipopolysaccharide-induced pulmonary inflammation.
Semicarbazide-sensitive amine oxidase (SSAO) resides on the vascular endothelium and smooth muscle cell surface and is capable of deaminating short chain aliphatic amines and producing toxic aldehydes and hydrogen peroxide. The enzyme, also known as a vascular adhesion protein-1, is involved in the inflammation process. This intriguing protein with dual functions is increased in the serum of diabetic and heart failure patients. In the present study we assessed the involvement of SSAO in a lipopolysaccharide-induced pulmonary inflammation model using transgenic mice that overexpress human vascular adhesion protein-1. Overexpression of SSAO activity increased the formation of protein-formaldehyde deposits in tissues. Lysine residues of proteins were the primary targets for cross-linkage with formaldehyde derived from deamination of methylamine. Lipo-polysaccharide-induced increases in inflammatory cells in the bronchoalveolar lavage (BAL) fluid were significantly higher in the transgenic than in the nontransgenic mice. BAL cell counts were also higher in the untreated transgenic than in nontransgenic mice. Blocking SSAO activity with a selective inhibitor significantly reduced the number of neutrophils as well as levels of macrophage inflammatory protein-1alpha, granulocyte colony-stimulating factor, tumor necrosis factor-alpha, and interleukin-6 in the BAL fluid. Inhalation of methylamine also increased BAL neutrophil counts. Together, these results suggest a role for SSAO-mediated deamination in pulmonary inflammation.
Yu
Peter H
PH
Department of Psychiatry, Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. yup@usask.ca
Lu
Li-Xin
LX
Fan
Hui
H
Kazachkov
Mychaylo
M
Jiang
Zhong-Jian
ZJ
Jalkanen
Sirpa
S
Stolen
Craig
C
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D054407:Chemokine CCL4; D003641:Deamination; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000633:toxicity; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008744:Methylamines / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D018410:Pneumonia, Bacterial / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015815:Cell Adhesion Molecules; D054407:Chemokine CCL4; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D008744:Methylamines; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; C027451:methylamine; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)