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IMP and AMP deaminase in reperfusion injury down-regulates neutrophil recruitment.

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IMP and AMP deaminase in reperfusion injury down-regulates neutrophil recruitment.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Qiu, F. H. Wada, K. Serhan, C. N. Stahl, G. L.
Description	Author Affiliation: Qiu FH ( Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.);
Abstract	We examined gene regulation in murine lungs after hind-limb vessel occlusion and reperfusion. A rapid increase of transcript for the AMP deaminase 3 gene (AMPD3) and its enzymatic activity (EC) generating inosine monophosphate (IMP) were identified with transcripts located in bronchial and alveolar epithelium. AMP deaminase inhibitor decreased IMP levels and significantly enhanced neutrophil recruitment within lung tissue during reperfusion. In addition, IMP inhibited cytokine-initiated neutrophil infiltration in vivo and selectively attenuated neutrophil rolling by 90% in microvessels. We prepared labeled IMP and demonstrated that IMP specifically binds to neutrophils. IMP also stimulated binding of gamma-[(35)S]thio-GTP, suggesting that IMP is a potent regulator of neutrophils. Taken together, these results elucidate a previously unrecognized mechanism that protects tissues from the potentially deleterious consequences of aberrant neutrophil accumulation. Moreover, they are relevant for new therapeutic approaches to regulate neutrophil responses in inflammation and vascular disease.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	8
Volume Number	97
Language	English
Publisher	National Academy of Sciences
Publisher Date	2000-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	AMP Deaminase Metabolism Down-Regulation Inosine Monophosphate Neutrophils Cytology Reperfusion Injury Enzymology Antagonists & Inhibitors Genetics Animals Binding Sites Cell Movement DNA Primers Enzyme Inhibitors Pharmacology Lung Pathology Lung Injury Mice Molecular Sequence Data RNA, Messenger Sequence Homology, Nucleic Acid Up-Regulation Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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