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Chemokine Involvement in Lung Injury Secondary to Ischaemia/Reperfusion

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Abstract

Introduction

During transplant surgeries, the lung experiences an ischaemia–reperfusion (I/R)-induced damage identified as a significant cause of morbidity and mortality. However, the mechanisms by which I/R induces leucocyte accumulation and subsequent tissue damage in lung surgeries remain unknown. Therefore, the present study aims to assess the role of monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein 2 (MIP-2) in leucocyte chemotaxis related to lung injury secondary to I/R.

Methods

Six pigs were subjected to an orthotopic left caudal lobe lung transplantation with a subsequent 60-min graft reperfusion (Transplant group). In addition, six animals underwent to sham surgery (Sham Group). Plasma samples and lung biopsies were collected before the beginning of pneumonectomy, before starting the reperfusion, and 30 min and 60 min after the beginning of the reperfusion. Plasma levels of intercellular adhesion molecule 1 (ICAM-1) and lung expressions of MCP-1, MIP-2, myeloperoxidase (MPO), and lung oedema were measured.

Results

Lung I/R caused substantial damage observed as pulmonary oedema. The oedema was evident after the ischemic insult and increased after reperfusion. After reperfusion, increased levels of MPO were observed which suggests an activation and infiltration of neutrophils into the lung tissue. After 30 min of reperfusion, MCP-1, MIP-2, and ICAM-1 levels were significantly increased compared to prepneumonectomy levels (p < 0.05) and a further increase was observed after 60 min of reperfusion (p < 0.05).

Conclusion

The present study demonstrates that activated neutrophils, as well as MCP-1, MIP-2, and ICAM-1, are involved in inflammatory response induced by ischaemia–reperfusion-induced lung injury.

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Acknowledgements

The authors would like to thank Medicine students Paula Corral, Aida Izquierdo and Guzmán López de Hontanar, and Pharmacy student Pedro Muñoz, for their continued interest and cooperation in our work. The skilful technical assistance of Ma.Angeles Ramírez-Alcázar, Cynthia Alarcón, Inés Hernández Fisac and Rocío Campón and Daniel Campón is also gratefully acknowledged.

Funding

This work was supported by Ministerio de Educación y Competitividad (Grants PI13/00700 and PI13/0002), Fundación Mutua Madrileña (FMM 14/08) and NEUMOMADRID (Neu 2010).

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Author notes

  1. Lisa Rancan and Sergio D. Paredes authors have contributed equally to this work. Carlos Simón and Elena Vara two senior authors have contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology III, School of Medicine, Complutense University of Madrid, Av.da Complutense s/n, 28040, Madrid, Spain

    Lisa Rancan, Jorge Guzmán & Elena Vara

  2. Department of Physiology, School of Medicine, Complutense University of Madrid, Madrid, Spain

    Sergio D. Paredes

  3. Service of Thoracic Surgery, Gregorio Marañón University General Hospital, Madrid, Spain

    Luis Huerta, Federico González-Aragoneses & Carlos Simón

  4. Service of Anaesthesiology and Rehabilitation, Gregorio Marañón University General Hospital, Madrid, Spain

    Javier Casanova & Ignacio Garutti

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  1. Lisa Rancan
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Correspondence to Lisa Rancan.

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Rancan, L., Paredes, S.D., Huerta, L. et al. Chemokine Involvement in Lung Injury Secondary to Ischaemia/Reperfusion. Lung 195, 333–340 (2017). https://doi.org/10.1007/s00408-017-0001-x

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  • DOI: https://doi.org/10.1007/s00408-017-0001-x

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