Linked Life Data

12554696

Source:http://linkedlifedata.com/resource/pubmed/id/12554696

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-1-29
pubmed:abstractText
Local cooling protects against TNF-alpha-induced injury by attenuating inflammation-associated microcirculatory dysfunction and leukocytic response. Mechanisms of protection, however, are not fully understood. We studied whether the metabolites of the HO and NOS pathway, exerting potent vasodilatory, antioxidant, and anti-apoptotic properties, are involved in tissue cryoprotection. In animals pretreated with L-NAME or SnPP-IX, cooling-associated abrogation of TNF-alpha-induced microcirculatory dysfunction was abolished. Combined L-NAME/SnPP-IX pretreatment did not cause greater blunting than seen when each mediator system was inhibited separately. In SnPP-IX- but not L-NAME-pretreated animals, transient hypothermia failed to reduce TNF-alpha-mediated leukocyte adherence. Vice versa, treatment of TNF-alpha-exposed animals with either the NO donor l-arginine or the HO-1 inductor hemin mimicked cooling-associated tissue protection except for failure of l-arginine to abrogate the inflammatory leukocyte response. The efficiency of cooling to inhibit TNF-alpha-induced apoptotic cell death was blunted in SnPP-IX-, L-NAME-, and SnPP-IX/L-NAME-pretreated animals. Coadministration of Trolox in SnPP-IX-treated animals partly attenuated leukocyte adherence and cell apoptosis, implying that the HO pathway metabolite biliverdin contributes to the salutary effects of cooling. Thus, our study provides evidence that metabolites of the HO and the NOS pathway mediate the cooling-associated protection of inflamed tissue. Biliverdin rather than CO and NO mediates the anti-inflammatory action, whereas a coordinated function of the gaseous monoxides prevents microcirculatory dysfunction and apoptotic cell death.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-85
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12554696-Animals, pubmed-meshheading:12554696-Apoptosis, pubmed-meshheading:12554696-Arginine, pubmed-meshheading:12554696-Blood Flow Velocity, pubmed-meshheading:12554696-Cell Adhesion, pubmed-meshheading:12554696-Cryotherapy, pubmed-meshheading:12554696-Enzyme Inhibitors, pubmed-meshheading:12554696-Female, pubmed-meshheading:12554696-Heme Oxygenase (Decyclizing), pubmed-meshheading:12554696-Hemin, pubmed-meshheading:12554696-Inflammation, pubmed-meshheading:12554696-Leukocytes, pubmed-meshheading:12554696-Male, pubmed-meshheading:12554696-Metalloporphyrins, pubmed-meshheading:12554696-Mice, pubmed-meshheading:12554696-Microcirculation, pubmed-meshheading:12554696-Muscle, Skeletal, pubmed-meshheading:12554696-NG-Nitroarginine Methyl Ester, pubmed-meshheading:12554696-Nitric Oxide, pubmed-meshheading:12554696-Protoporphyrins, pubmed-meshheading:12554696-Skin, pubmed-meshheading:12554696-Tumor Necrosis Factor-alpha
pubmed:year
2003
pubmed:articleTitle
Heme oxygenase and nitric oxide synthase mediate cooling-associated protection against TNF-alpha-induced microcirculatory dysfunction and apoptotic cell death.
pubmed:affiliation
Institute for Clinical and Experimental Surgery, University of Saarland, D-66421 Homburg/Saar, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't