Bone marrow‐derived mesenchymal stromal cells rescue alveolar mitochondrial function in lipopolysaccharide‐treated mice

In lipopolysaccharide (LPS)‐induced acute lung injury (ALI), lung mitochondria are dysfunctional. Bone marrow‐derived mesenchymal stromal cells (MSCs) may protect against ALI by rescuing mitochondrial function. To determine mitochondrial function as denoted by ATP levels in alveolar epithelial (AE) cells in situ , we transfected alveoli with a GFP‐based, ATP probe (Perceval). The groups were: untreated, LPS alone (i.t. 1 mg/kg)), LPS plus MSCs (i.t. 2x10 5 cells). The MSCs expressed red fluorescence of mitochondria‐targeted, DsRed protein. After 24 hours, we isolated and blood‐perfused lungs and viewed alveoli by confocal microscopy. For untreated, ATP fluorescence was 150±5 grey levels in AE cells, indicating successful Perceval expression. In LPS alone, AE ATP fluorescence was 75±3% of untreated (P<0.05). In LPS plus MSCs, ATP fluorescence was not different from untreated. Hyperinflation‐induced surfactant secretion, an ATP‐dependent response, was absent for LPS alone (P<0.05), but present for untreated and LPS plus MSCs (P<0.05). Our data indicate that in AE cells, LPS decreased ATP and blocked inflation‐induced surfactant secretion. Both responses were reversed by MSCs. We conclude, MSCs rescued ATP production and ATP‐dependent surfactant secretion in alveoli of LPS‐treated mice. By restoring alveolar mitochondrial function, MSCs may rescue overall lung function in sepsis (support HL64896).