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Beta-chemokine function in experimental lung ischemia-reperfusion injury.
Ann Thorac Surg. 2004 Mar; 77(3):1056-62.AT

Abstract

BACKGROUND

Although chemokines are functionally important in models of ischemia-reperfusion injury, little is known about their role in lung ischemia-reperfusion injury (LIRI). This study examined the role of the beta-chemokines, macrophage inflammatory protein (MIP)-1alpha, monocyte chemoattractant protein (MCP)-1, and regulated upon activation normal T cells expressed and secreted (RANTES) in LIRI.

METHODS

Left lungs of Long-Evans rats underwent normothermic ischemia for 90 minutes and reperfusion for up to 4 hours. Treated animals received anti-MIP-1alpha, anti-MCP-1, or anti-RANTES antibodies before reperfusion. Changes in lung vascular permeability were measured with iodine 125-labeled bovine serum albumin. Neutrophil accumulation in the lung parenchyma was determined by myeloperoxidase activity, and bronchoalveolar lavage was performed to measure leukocyte cell counts. Western blots, Northern blots, and ribonuclease protection assays assessed beta-chemokine messenger RNA and protein levels.

RESULTS

Animals receiving anti-MIP-1alpha demonstrated reduced vascular permeability compared with controls (p < 0.001). Attenuation of permeability was less dramatic in animals treated with anti-MCP-1 and anti-RANTES antibody, which demonstrated permeability decreases of 15% and 16%, respectively (p < 0.02). Lung neutrophil accumulation was reduced in animals receiving anti-MIP-1alpha antibody (p < 0.005) but was unchanged in animals receiving either anti-MCP-1 or anti-RANTES. Bronchoalveolar lavage leukocyte content was also reduced by treatment with anti-MIP-1alpha (p < 0.003) and was unchanged in anti-MCP-1-treated and anti-RANTES-treated animals. MIP-1alpha treatment decreased tumor necrosis factor-alpha messenger RNA in injured left lungs.

CONCLUSIONS

MIP-1alpha is functionally significant in the development of LIRI. It likely exerts its effects in part by mediating the expression of proinflammatory and antiinflammatory cytokines and influencing tissue neutrophil recruitment. MCP-1 and RANTES seem to play relatively minor roles in the development of direct LIRI.

Authors+Show Affiliations

Krishnadasan B
Department of Surgery, Division of Cardiothoracic Surgery, University of Washington Medical Center, Seattle, Washington, USA.
Farivar AS
No affiliation info available
Naidu BV
No affiliation info available
Woolley SM
No affiliation info available
Byrne K
No affiliation info available
Fraga CH
No affiliation info available
Mulligan MS
No affiliation info available

MeSH

AnimalsAntibodiesBlotting, NorthernBlotting, WesternBronchoalveolar Lavage FluidCapillary PermeabilityChemokine CCL2Chemokine CCL3Chemokine CCL4Chemokine CCL5Chemokines, CCLeukocyte CountLung DiseasesMacrophage Inflammatory ProteinsNeutrophil InfiltrationPeroxidaseRNARatsRats, Long-EvansReperfusion Injury

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14992926

Citation

Krishnadasan, Baiya, et al. "Beta-chemokine Function in Experimental Lung Ischemia-reperfusion Injury." The Annals of Thoracic Surgery, vol. 77, no. 3, 2004, pp. 1056-62.
Krishnadasan B, Farivar AS, Naidu BV, et al. Beta-chemokine function in experimental lung ischemia-reperfusion injury. Ann Thorac Surg. 2004;77(3):1056-62.
Krishnadasan, B., Farivar, A. S., Naidu, B. V., Woolley, S. M., Byrne, K., Fraga, C. H., & Mulligan, M. S. (2004). Beta-chemokine function in experimental lung ischemia-reperfusion injury. The Annals of Thoracic Surgery, 77(3), 1056-62.
Krishnadasan B, et al. Beta-chemokine Function in Experimental Lung Ischemia-reperfusion Injury. Ann Thorac Surg. 2004;77(3):1056-62. PubMed PMID: 14992926.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Beta-chemokine function in experimental lung ischemia-reperfusion injury. AU - Krishnadasan,Baiya, AU - Farivar,Alexander S, AU - Naidu,Babu V, AU - Woolley,Steven M, AU - Byrne,Karen, AU - Fraga,Charles H, AU - Mulligan,Michael S, PY - 2003/08/07/accepted PY - 2004/3/3/pubmed PY - 2004/4/9/medline PY - 2004/3/3/entrez SP - 1056 EP - 62 JF - The Annals of thoracic surgery JO - Ann Thorac Surg VL - 77 IS - 3 N2 - BACKGROUND: Although chemokines are functionally important in models of ischemia-reperfusion injury, little is known about their role in lung ischemia-reperfusion injury (LIRI). This study examined the role of the beta-chemokines, macrophage inflammatory protein (MIP)-1alpha, monocyte chemoattractant protein (MCP)-1, and regulated upon activation normal T cells expressed and secreted (RANTES) in LIRI. METHODS: Left lungs of Long-Evans rats underwent normothermic ischemia for 90 minutes and reperfusion for up to 4 hours. Treated animals received anti-MIP-1alpha, anti-MCP-1, or anti-RANTES antibodies before reperfusion. Changes in lung vascular permeability were measured with iodine 125-labeled bovine serum albumin. Neutrophil accumulation in the lung parenchyma was determined by myeloperoxidase activity, and bronchoalveolar lavage was performed to measure leukocyte cell counts. Western blots, Northern blots, and ribonuclease protection assays assessed beta-chemokine messenger RNA and protein levels. RESULTS: Animals receiving anti-MIP-1alpha demonstrated reduced vascular permeability compared with controls (p < 0.001). Attenuation of permeability was less dramatic in animals treated with anti-MCP-1 and anti-RANTES antibody, which demonstrated permeability decreases of 15% and 16%, respectively (p < 0.02). Lung neutrophil accumulation was reduced in animals receiving anti-MIP-1alpha antibody (p < 0.005) but was unchanged in animals receiving either anti-MCP-1 or anti-RANTES. Bronchoalveolar lavage leukocyte content was also reduced by treatment with anti-MIP-1alpha (p < 0.003) and was unchanged in anti-MCP-1-treated and anti-RANTES-treated animals. MIP-1alpha treatment decreased tumor necrosis factor-alpha messenger RNA in injured left lungs. CONCLUSIONS: MIP-1alpha is functionally significant in the development of LIRI. It likely exerts its effects in part by mediating the expression of proinflammatory and antiinflammatory cytokines and influencing tissue neutrophil recruitment. MCP-1 and RANTES seem to play relatively minor roles in the development of direct LIRI. SN - 0003-4975 UR - https://www.unboundmedicine.com/medline/citation/14992926/Beta_chemokine_function_in_experimental_lung_ischemia_reperfusion_injury_ DB - PRIME DP - Unbound Medicine ER -