PMID- 14734138
OWN - NLM
STAT- MEDLINE
DCOM- 20040506
LR  - 20190922
IS  - 1053-2498 (Print)
IS  - 1053-2498 (Linking)
VI  - 23
IP  - 1
DP  - 2004 Jan
TI  - Novel broad-spectrum chemokine inhibitor protects against lung 
      ischemia-reperfusion injury.
PG  - 128-34
AB  - BACKGROUND: Functional roles for chemokines have been demonstrated in several 
      models of ischemia-reperfusion injury. The redundancy inherent to chemokine 
      pathways makes administration of neutralizing antibodies to any single chemokine 
      ineffective in ameliorating injury. This study was undertaken to define the 
      pattern of chemokine expression in lung ischemia-reperfusion injury (LIRI), and 
      to determine whether a broad-spectrum chemokine inhibitor, NR58-3.14.3, could 
      confer significant protection against LIRI. METHODS: Left lungs of rats were 
      rendered ischemic for 90 minutes and then reperfused for 4 hours. Chemokine 
      secretion into the alveolar space was quantified by enzyme-linked immunoassay. 
      Treated animals received NR58-3.14.3 prior to reperfusion. Vascular injury was 
      measured by lung permeability index, neutrophil accumulation in lung parenchyma 
      was determined by myeloperoxidase (MPO) activity, and alveolar leukocyte counts 
      were quantified in bronchoalveolar lavage (BAL) effluent. A ribonuclease 
      protection assay evaluated mRNA expression of various chemokines. RESULTS: Lavage 
      effluent in untreated animals demonstrated significant increases in the secretion 
      of cytokine-induced neutrophil chemoattractant (CINC), tumor necrosis 
      factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), MIP-1alpha 
      and monocyte chemoattractant protein-1 (MCP-1). Animals receiving NR58-3.14.3 
      demonstrated a 37% (p < 0.001) reduction in vascular injury and a marked 
      reduction in lung MPO activity (p < 0.001) and alveolar cell counts (p = 0.005). 
      Chemokine inhibition decreased mRNA expression of a number of early response 
      cytokines when compared with positive control animals, and caused a significant 
      decrease (p < 0.04) in the secretion of TNF-alpha. CONCLUSIONS: These studies 
      demonstrate that chemokines are expressed after lung ischemia and reperfusion, 
      and that broad-spectrum chemokine inhibition ameliorates reperfusion injury. mRNA 
      expression of early response cytokines was modulated, and the secretion of 
      TNF-alpha was decreased.
FAU - Naidu, Babu V
AU  - Naidu BV
AD  - Department of Surgery, University of Washington, Seattle, Washington 98195, USA.
FAU - Farivar, Alexander S
AU  - Farivar AS
FAU - Woolley, Steven M
AU  - Woolley SM
FAU - Grainger, David
AU  - Grainger D
FAU - Verrier, Edward D
AU  - Verrier ED
FAU - Mulligan, Michael S
AU  - Mulligan MS
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Chemokines, CC)
RN  - 0 (Peptides, Cyclic)
RN  - 0 
      (cyclo(cysteinyl-glutaminyl-isoleucyl-tryptophyl-lysyl-glutaminyl-lysyl-prolyl-aspartyl-leucyl-cysteinyl-amide))
SB  - IM
MH  - Animals
MH  - Chemokines, CC/*antagonists & inhibitors
MH  - Disease Models, Animal
MH  - Lung/*blood supply
MH  - Macrophages, Alveolar/drug effects/immunology
MH  - Male
MH  - Neutrophils/drug effects/immunology
MH  - Peptides, Cyclic/pharmacology/*therapeutic use
MH  - Rats
MH  - Rats, Long-Evans
MH  - Reperfusion Injury/immunology/*prevention & control
EDAT- 2004/01/22 05:00
MHDA- 2004/05/07 05:00
CRDT- 2004/01/22 05:00
PHST- 2004/01/22 05:00 [pubmed]
PHST- 2004/05/07 05:00 [medline]
PHST- 2004/01/22 05:00 [entrez]
AID - S1053249803001025 [pii]
AID - 10.1016/s1053-2498(03)00102-5 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2004 Jan;23(1):128-34. doi: 
      10.1016/s1053-2498(03)00102-5.