Surfactant protein-A and toll-like receptor-4 modulate immune functions of preterm baboon lung dendritic cell precursor cells
2011
Awasthi, Shanjana | Madhusoodhanan, Rakhesh | Wolf, Roman
Lung infections are important risk factors for an increased morbidity and mortality in prematurely-delivered babies. Immaturity of the innate immune components makes them extremely susceptible to infection. Recently, we isolated lung dendritic cell (DC)-precursor cells from preterm fetal baboons. The isolated cells were found to be defective in phagocytosing Escherichia coli under basal conditions. In this study, we investigated the effects of exogenously-added purified native lung surfactant protein (SP)-A and recombinant toll-like receptor (TLR)-4-MD2 proteins on phagocytic uptake and cytokine secreting ability of fetal baboon lung DC-precursor cells. The cells were pulsed with SP-A and/or TLR4-MD2 proteins and the phagocytic function was investigated by incubating the cells with fluorescent-labeled E. coli bioparticles and analyzed by spectrofluorometry. The amounts of TNF-α secreted in cell-free supernatants were measured by ELISA. Our results demonstrate that SP-A and TLR4-MD2 proteins, whether added alone or together, induce phagocytosis of E. coli (p<0.05). The SP-A does not affect TNF-α secretion, while the TLR4-MD2 protein induces TNF-α. However, simultaneous addition of SP-A with TLR4-MD2 protein reduces the TLR4-MD2-protein induced TNF-α to basal level. In conclusion, our results indicate that an exogenous administration of SP-A can potentially induce phagocytic activity and anti-inflammatory effect in preterm babies, and help control infection and inflammation.
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