Source:http://linkedlifedata.com/resource/pubmed/id/15123771
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2004-6-30
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| pubmed:abstractText |
Polymorphonuclear neutrophil (PMN) extravasation/sequestration in the lung and a dysregulated inflammatory response characterize the pathogenesis of acute lung injury (ALI). Previously, we have shown that hemorrhage (Hem) serves to prime PMN such that subsequent septic challenge [cecal ligation and puncture (CLP)] produces a pathological, inflammatory response and consequent lung injury in mice. Keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 (MIP-2) are murine CXC chemokines found elevated in the lungs and plasma following Hem/CLP and have been reported by others to share a common receptor (CXCR2). Based on these data, we hypothesize that blockade of CXCR2 immediately following Hem would suppress KC and MIP-2 priming of PMN, thereby reducing the inflammatory injury observed following CLP. To assess this, Hem mice (90 min at 35+/-5 mmHg) were randomized to receive 0, 0.4, or 1 mg antileukinate (a hexapeptide inhibitor of CXCRs) in 100 microl phosphate-bufferd saline (PBS)/mouse subcutaneously, immediately following resuscitation (Ringer's lactate-4x drawn blood volume). Twenty-four hours post-Hem, mice were subjected to CLP and killed 24 h later. The results show that blockade of CXCR2 significantly (P<0.05, Tukey's test) reduced PMN influx, lung protein leak, and lung-tissue content of interleukin (IL)-6, KC, and MIP-2 and increased tissue IL-10 levels. Plasma IL-6 was significantly decreased, and IL-10 levels increased in a dose-dependent manner compared with PBS-treated mice. A differential effect was observed in plasma levels of KC and MIP-2. KC showed a significant reduction at the 0.4 mg antileukinate dose. In contrast, plasma MIP-2 was significantly elevated at both doses compared with the PBS-treated controls. Together, these data demonstrate that blockade of CXCR2 signaling attenuates shock-induced priming and ALI observed following Hem and subsequent septic challenge in mice.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0741-5400
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
76
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
58-64
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15123771-Animals,
pubmed-meshheading:15123771-Cecum,
pubmed-meshheading:15123771-Chemokines,
pubmed-meshheading:15123771-Disease Models, Animal,
pubmed-meshheading:15123771-Hemorrhage,
pubmed-meshheading:15123771-Immunohistochemistry,
pubmed-meshheading:15123771-Inflammation,
pubmed-meshheading:15123771-Ligation,
pubmed-meshheading:15123771-Mice,
pubmed-meshheading:15123771-Neutrophil Infiltration,
pubmed-meshheading:15123771-Neutrophils,
pubmed-meshheading:15123771-Oligopeptides,
pubmed-meshheading:15123771-Receptors, Interleukin-8B,
pubmed-meshheading:15123771-Respiratory Distress Syndrome, Adult,
pubmed-meshheading:15123771-Sepsis
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| pubmed:year |
2004
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| pubmed:articleTitle |
CXCR2 inhibition suppresses hemorrhage-induced priming for acute lung injury in mice.
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| pubmed:affiliation |
Aldrich 227, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA. AAYALA@LIFESPAN.org
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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