PMID- 22423062 OWN - NLM STAT- MEDLINE DCOM- 20120619 LR - 20131121 IS - 1873-734X (Electronic) IS - 1010-7940 (Linking) VI - 41 IP - 4 DP - 2012 Apr TI - Modulation of monocyte chemoattractant protein-1 expression by ischaemic preconditioning in a lung autotransplant model. PG - 933-9 LID - 10.1093/ejcts/ezr049 [doi] AB - OBJECTIVES: Monocyte chemoattractant protein-1 (MCP-1) is believed to play a crucial role in lung ischaemia-reperfusion injury (LIRI). Ischaemic preconditioning (IP) has been shown to protect several organs from ischaemia-reperfusion (IR) injury, although less is known about IP's effect on MCP-1 modulation. The objective of this study was to investigate IP's effect on MCP-1 expression in lung tissue and its relationship with oxidative stress and proinflammatory cytokine production in an experimental LIRI model. METHODS: Two groups (IP and control groups) of seven large white pigs underwent a lung autotransplant (left pneumonectomy, ex situ superior lobectomy and lower lobe reimplantation). Before pneumonectomy was performed in the study group, IP was induced with two cycles of 5 min of left pulmonary artery occlusion with a 5 min interval of reperfusion between the two occlusions. Blood samples and lung biopsies were obtained at prepneumonectomy (PPn), at prereperfusion (PRp) and up to 30 min after reperfusion of the implanted lobe (Rp-10' and Rp-30'). Haemodynamic and blood-gas measurements, evaluation of oxidative stress in lung tissue and MCP-1, tumour necrosis factor-alpha (TNF-alpha) and IL-1 protein and mRNA measurements in lung tissue were performed. Nonparametric tests were used to compare differences between groups. Data are expressed as mean +/- SEM. RESULTS: In control lungs, MCP-1 protein levels were found to be higher at PRp, Rp-10' and Rp-30' than at PPn (0.59 +/- 0.1 vs. 0.21 +/- 0.05, 0.47 +/- 0.01 vs. 0.21 +/- 0.05 and 0.56 +/- 0.01 vs. 0.21 +/- 0.05, respectively; P < 0.05). These differences were not evident in the IP group. MCP-1 levels at PRp, Rp-10' and Rp-30' were significantly higher in the control group than in the IP group (0.59 +/- 0.1 vs. 0.15 +/- 0.02, 0.47 +/- 0.01 vs. 0.13 +/- 0.01 and 0.56 +/- 0.01 vs. 0.27 +/- 0.01, respectively; P < 0.05). MCP-1, TNF-alpha and IL-1 mRNA expressions were lower at PRp, Rp-10' and Rp-30' (control vs. IP group, P < 0.05) when IP was carried out. Lipid peroxidation metabolites and myeloperoxidase activity increase in lung tissue were prevented by IP. CONCLUSIONS: In this model, LIRI induced the expression of MCP-1 and the proinflammatory proteins TNF-alpha and IL-1 in control lungs. IP significantly reduced the expression of these chemokines and cytokines. These features may explain the reduction of oxidative stress observed with IP. FAU - Simon, Carlos AU - Simon C AD - Department of Thoracic Surgery, Gregorio Maranon University General Hospital, Madrid, Spain. carlosmsa@telefonica.net FAU - Vara, Elena AU - Vara E FAU - Garutti, Ignacio AU - Garutti I FAU - Gonzalez-Casaurran, Guillermo AU - Gonzalez-Casaurran G FAU - Azcarate, Leire AU - Azcarate L FAU - Isea, Jesus AU - Isea J FAU - Huerta, Luis AU - Huerta L FAU - Gonzalez-Aragoneses, Federico AU - Gonzalez-Aragoneses F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111116 PL - Germany TA - Eur J Cardiothorac Surg JT - European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery JID - 8804069 RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (RNA, Messenger) RN - EC 1.11.1.7 (Peroxidase) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Chemokine CCL2/*metabolism MH - Cytokines/biosynthesis/genetics MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay/methods MH - Gene Expression Regulation/physiology MH - Hemodynamics/physiology MH - Inflammation Mediators/metabolism MH - Ischemic Preconditioning/*methods MH - Lung/*metabolism MH - *Lung Transplantation MH - Oxidative Stress/physiology MH - Oxygen/blood MH - Partial Pressure MH - Peroxidase/metabolism MH - RNA, Messenger/genetics MH - Reperfusion Injury/metabolism/prevention & control MH - Sus scrofa EDAT- 2012/03/17 06:00 MHDA- 2012/06/20 06:00 CRDT- 2012/03/17 06:00 PHST- 2012/03/17 06:00 [entrez] PHST- 2012/03/17 06:00 [pubmed] PHST- 2012/06/20 06:00 [medline] AID - ezr049 [pii] AID - 10.1093/ejcts/ezr049 [doi] PST - ppublish SO - Eur J Cardiothorac Surg. 2012 Apr;41(4):933-9. doi: 10.1093/ejcts/ezr049. Epub 2011 Nov 16.