Intratracheal instillation of alveolar type II cells enhances recovery from acute lung injury in rats

Raquel Guillamat-Prats, Ferranda Puig, Marta Camprubí-Rimblas, Raquel Herrero, Anna Serrano-Mollar, Maria Nieves Gómez, Jessica Tijero, Michael A. Matthay, Lluís Blanch, Antonio Artigas

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

© 2017 International Society for the Heart and Lung Transplantation Background: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by excess production of inflammatory factors. Alveolar type II (ATII) cells help repair damaged lung tissue, rapidly proliferating and differentiating into alveolar type I cells after epithelial cell injury. In ALI, the lack of viable ATII favors progression to more severe lung injury. ATII cells regulate the immune response by synthesizing surfactant and other anti-inflammatory proteins and lipids. Cross-talk between ATII and other cells such as macrophages may also be part of the ATII function. The aim of this study was to test the anti-inflammatory and reparative effects of ATII cells in an experimental model of ALI. Methods: In this study ATII cells (2.5 × 106 cells/animal) were intratracheally instilled in rats with HCl and lipopolysaccharide (LPS)-induced ALI and in healthy animals to check for side effects. The specific effect of ATII cells was compared with fibroblast transplantation. Results: ATII cell transplantation promoted recovery of lung function, decrease mortality and lung inflammation of the animals with ALI. The primary mechanisms for benefit were paracrine effects of prostaglandin E2 (PGE2) and surfactant protein A (SPA) released from ATII cells that modulate alveolar macrophages to an anti-inflammatory phenotype. To our knowledge, these data are the first to provide evidence that ATII cells secrete PGE2 and SPA, reducing pro-inflammatory macrophage activation and ALI. Conclusion: ATII cells and their secreted molecules have shown an ability to resolve ALI, thereby highlighting a potential novel therapeutic target.
Original languageEnglish
Pages (from-to)782-791
JournalJournal of Heart and Lung Transplantation
Volume37
Issue number6
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • acute lung injury
  • acute respiratory distress syndrome
  • alveolar type II cells
  • cell therapy
  • macrophages

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