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Alpha chemokines regulate direct lung ischemia-reperfusion injury.
J Heart Lung Transplant. 2004 May; 23(5):585-91.JH

Abstract

BACKGROUND

Alpha chemokines function predominantly to recruit and activate neutrophils, which are important effectors of acute lung injury. This study evaluated whether blockade of 2 potent alpha chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC), is protective against lung ischemia-reperfusion injury in a warm in situ hilar clamp model.

METHODS

Left lungs of Long-Evans rats underwent normothermic ischemia for 90 minutes and reperfusion for up to 4 hours. Treated animals received antibodies to MIP-2 or CINC immediately prior to reperfusion. Lung injury was quantitated by vascular permeability to (125)I-radiolabeled bovine serum albumin, lung tissue neutrophil sequestration (myeloperoxidase [MPO] content), and alveolar leukocyte content in bronchoalveolar lavage (BAL) fluid. CINC and MIP-2 mRNA expression were assessed by northern blot, while ribonuclease protection assays were performed to evaluate mRNA expression for a number of early response cytokines. MIP-2 and CINC protein expression in injured lungs was determined by immunoblotting.

RESULTS

Treatment with antibodies to CINC or MIP-2 was associated with significant protection against increases in vascular permeability, MPO content and alveolar leukocyte sequestration in injured lungs. Expression of CINC and MIP-2 mRNA peaked after 2 hours of reperfusion in injured lungs, and protein levels were evident on immunoblotting after 3 hours of reperfusion. Neither CINC nor MIP-2 blockade appeared to modulate cytokine mRNA expression.

CONCLUSIONS

CINC and MIP-2 are important mediators involved in direct lung ischemia-reperfusion injury. They appear to function by modulating neutrophil recruitment, but not inflammatory cytokine release.

Authors+Show Affiliations

Farivar AS
University of Washington Medical Center, Division of Cardiothoracic Surgery, Seattle, Washington 98195, USA.
Krishnadasan B
No affiliation info available
Naidu BV
No affiliation info available
Woolley SM
No affiliation info available
Verrier ED
No affiliation info available
Mulligan MS
No affiliation info available

MeSH

AnimalsBlotting, NorthernBlotting, WesternBronchoalveolar LavageCapillary PermeabilityChemokine CXCL2Chemokines, CXCDisease Models, AnimalIntercellular Signaling Peptides and ProteinsLungPeroxidaseRatsRats, Long-EvansReperfusion Injury

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15135375

Citation

Farivar, Alexander S., et al. "Alpha Chemokines Regulate Direct Lung Ischemia-reperfusion Injury." The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, vol. 23, no. 5, 2004, pp. 585-91.
Farivar AS, Krishnadasan B, Naidu BV, et al. Alpha chemokines regulate direct lung ischemia-reperfusion injury. J Heart Lung Transplant. 2004;23(5):585-91.
Farivar, A. S., Krishnadasan, B., Naidu, B. V., Woolley, S. M., Verrier, E. D., & Mulligan, M. S. (2004). Alpha chemokines regulate direct lung ischemia-reperfusion injury. The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, 23(5), 585-91.
Farivar AS, et al. Alpha Chemokines Regulate Direct Lung Ischemia-reperfusion Injury. J Heart Lung Transplant. 2004;23(5):585-91. PubMed PMID: 15135375.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha chemokines regulate direct lung ischemia-reperfusion injury. AU - Farivar,Alexander S, AU - Krishnadasan,Baiya, AU - Naidu,Babu V, AU - Woolley,Steven M, AU - Verrier,Edward D, AU - Mulligan,Michael S, PY - 2003/02/28/received PY - 2003/05/12/revised PY - 2003/06/04/accepted PY - 2004/5/12/pubmed PY - 2004/9/25/medline PY - 2004/5/12/entrez SP - 585 EP - 91 JF - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JO - J Heart Lung Transplant VL - 23 IS - 5 N2 - BACKGROUND: Alpha chemokines function predominantly to recruit and activate neutrophils, which are important effectors of acute lung injury. This study evaluated whether blockade of 2 potent alpha chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC), is protective against lung ischemia-reperfusion injury in a warm in situ hilar clamp model. METHODS: Left lungs of Long-Evans rats underwent normothermic ischemia for 90 minutes and reperfusion for up to 4 hours. Treated animals received antibodies to MIP-2 or CINC immediately prior to reperfusion. Lung injury was quantitated by vascular permeability to (125)I-radiolabeled bovine serum albumin, lung tissue neutrophil sequestration (myeloperoxidase [MPO] content), and alveolar leukocyte content in bronchoalveolar lavage (BAL) fluid. CINC and MIP-2 mRNA expression were assessed by northern blot, while ribonuclease protection assays were performed to evaluate mRNA expression for a number of early response cytokines. MIP-2 and CINC protein expression in injured lungs was determined by immunoblotting. RESULTS: Treatment with antibodies to CINC or MIP-2 was associated with significant protection against increases in vascular permeability, MPO content and alveolar leukocyte sequestration in injured lungs. Expression of CINC and MIP-2 mRNA peaked after 2 hours of reperfusion in injured lungs, and protein levels were evident on immunoblotting after 3 hours of reperfusion. Neither CINC nor MIP-2 blockade appeared to modulate cytokine mRNA expression. CONCLUSIONS: CINC and MIP-2 are important mediators involved in direct lung ischemia-reperfusion injury. They appear to function by modulating neutrophil recruitment, but not inflammatory cytokine release. SN - 1053-2498 UR - https://www.unboundmedicine.com/medline/citation/15135375/Alpha_chemokines_regulate_direct_lung_ischemia_reperfusion_injury_ DB - PRIME DP - Unbound Medicine ER -