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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bucci, Mariarosaria Parente, Luca Ignarro, Louis J. Cirino, Giuseppe Roviezzo, Fiorentina Sessa, William C. Yu, Jun Posadas, Inmaculada |
| Description | Author Affiliation: Bucci M ( Dipartimento di Farmacologia Sperimentale, Via Domenico Montesano 49, Università di Napoli-Federico II, 80131 Naples, Italy.); |
| Abstract | The role of endothelium-derived nitric oxide (NO) in acute inflammation is not known. Here, we examine acute inflammation in congenic endothelial NO synthase-deficient (eNOS-/-) mice. Intraplantar injection of carrageenan induces a biphasic inflammatory response. The early phase (0-6 h) is largely eliminated, and the secondary phase (24-96 h) is markedly reduced in eNOS-/- but not WT mice. Inhibition of phosphatidylinositol 3-kinase or hsp90, pathways upstream of eNOS activation, also reduces carrageenan-stimulated edema formation. To separate the ability of eNOS to regulate leukocyte trafficking vs. vascular permeability, zymosan-stimulated leukocyte infiltration and protein extravasation were assessed in WT and eNOS-/- mice. Zymosan increases inflammatory cell extravasation to the same extent in WT and eNOS-/- mice, whereas the extravasation of plasma protein is lower in eNOS-/- mice. Inhibition of phosphatidylinositol 3-kinase and hsp90 also blocks protein leakage, but not leukocyte influx. These data collectively support the critical role for eNOS in regulating the magnitude of the acute inflammatory response and show that eNOS is critical for regulating microcirculatory endothelial barrier function in vivo. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 3 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Endothelium, Vascular Pathology Inflammation Etiology Nitric Oxide Synthase Metabolism Physiology Permeability Acute Disease Animals Carrageenan Pharmacology Chemotaxis, Leukocyte Mice Mice, Inbred C57BL Mice, Knockout Deficiency Nitric Oxide Synthase Type II Nitric Oxide Synthase Type III Signal Transduction Zymosan Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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