Age specific differences in murine alveolar endothelial cells to pathological conditions

Abstract

Abstract Neonatal pulmonary viral infections can have diverse outcomes ranging from bronchiolitis and pneumonia in RSV infection to more subdued response in SARS-CoV-2 infection. In this study, we investigated the responses of murine alveolar endothelial cells (MLEC) to neonate mice serum in presence of TLR agonists-treated macrophages, which can mimic SARS-Cov2 induced innate cell activation. We found that when poly I:C and ssRNA40 activated macrophages were cocultured with neonatal mice serum-treated MLECs, the expression of TNFα and IL-6 were significantly decreased. Moreover, macrophage co-culture leads to decreased ACE2 and VEGFR2 in adult MLECs, but macrophage co-culture increased ACE2 expression in neonatal MLECs under Poly I:C but not ssRNA40 stimulation. Addition of neonatal mice serum to MLECs increases the reactive oxygen species but downregulates multiple inflammatory signal pathways. Concurrently, the expression VE-cadherin and Shp2 was downregulated in neonatal mice serum exposed MLECs, which leads to compromised MLEC barrier integrity. Morphologically, neonatal mice serum, but not adult mice serum, triggered the lipid droplets formation and upregulated SR-BI and CD36 receptor expression in MLECs. Taken together, neonatal and adult MLECs differentially regulate cytokine-secretion from activated macrophages, and neonatal serum breaks the tight cell junction between MLECs by down regulating Shp2 and VE-Cadherin expression and induces the lipid droplets formation in MLECs through receptors SR-BI and CD36. The differences in neonatal and adult MLEC responses to pathologic conditions may reflect the age specific pulmonary manifestations to viral infections.