The Role of Pericytes in Lipopolysaccharide-Induced Murine Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome that is most commonly triggered by infection-related inflammation. Lung pericytes can respond to infection and act as immune and proangiogenic cells; moreover, these cells can differentiate into myofibroblasts in non-resolving ARDS and contribute to the development of pulmonary fibrosis. Here, we aimed to characterize the role of lung cells which present characteristic of pericytes, such as peri-endothelial location and expression of panel of specific markers. To study their role in ARDS we used a murine model of lipopolysaccharide induced (LPS) resolving ARDS. We confirmed the development of ARDS after LPS instillation which was resolved 14 days after onset. Using immunofluorescence and flow cytometry we observed early expansion of NG2+PDGFRβ+ pericytes in murine lungs with loss of CD31+ PDGFRβ+ endothelial cells. These changes were accompanied by specific changes in lung structure and loss of vascular integrity. On day 14 after ARDS onset the composition of pericytes and endothelial cells returned to baseline values. LPS-induced ARDS activated NOTCH signaling in lung pericytes, the inhibition of which during LPS stimulation reduced the expression of its downstream target genes, pericyte markers and angiogenic factors. Together, lung pericytes in response to inflammatory injury activate NOTCH signaling that supports their maintenance and in turn can contribute to recovery of the microvascular endothelium.