Intratracheal instillation of alveolar type II cells enhances recovery from acute lung injury in rats.
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.
['Guillamat-Prats|Raquel|R|', 'Puig|Ferranda|F|', 'Camprubí-Rimblas|Marta|M|', 'Herrero|Raquel|R|', 'Serrano-Mollar|Anna|A|', 'Gómez|Maria Nieves|MN|', 'Tijero|Jessica|J|', 'Matthay|Michael A|MA|', 'Blanch|Lluís|L|', 'Artigas|Antonio|A|']
D055371:Acute Lung Injury D056809:Alveolar Epithelial Cells D000818:Animals D017690:Cell Transplantation D008297:Male D051381:Rats D017207:Rats, Sprague-Dawley D012074:Remission Induction D014132:Trachea
alveolar type II cells acute lung injury acute respiratory distress syndrome macrophages cell therapy