BACKGROUND: Exogenous surfactant has been accepted worldwide as a therapy of RDS in premature and term infants. Exogenous surfactant is usually derived from lung extracts containing phospholipids and the surfactant proteins SP-B and SP-C. Synthetic peptides of SP-B and SP-C are being tested with the aim to develop a completely synthetic surfactant preparation. Nevertheless, the effects of these peptides on the endogenous surfactant metabolism remain unknown. OBJECTIVES: The effect of synthetic SP-B peptides on uptake of surfactant-like liposomes was investigated in alveolar cells. Native SP-B and seven SP-B peptides were included: monomeric and dimeric SP-B(1-25) (Cys-11 --> Ala-11), SP-B(63-78)and Ala-SP-B(63-78) (Cys-71 --> Ala-71;Cys-77 --> Ala-77)and their serine mutants. METHODS: In vitro, alveolar macrophages (AM) and alveolar type II cells (ATII) were incubated with liposomes containing SP-B or one of its peptides. In vivo, rats received intratracheally various SP-B peptides (SP-B/lipid ratio 1:33 w/w) incorporated in fluorescent surfactant-like liposomes. One hour after instillation, AM and ATII were isolated and cell-associated fluorescence was determined using flow cytometry. Confocal laser microscopy was performed to ensure internalization of the liposomes. RESULTS: In vitro uptake by AM or ATII was not influenced by the SP-B peptides. In vivo, SP-B(1-25) and Ser-SP-B(1-25) increased the uptake by AM whereas dSP-B(1-25) decreased the uptake. Neither SP-B(1-25) nor dSP-B(1-25 )affected total uptake by ATII. The overall uptake by SP-B(63-78) variants was not changed. CONCLUSIONS: Surface-active synthetic SP-B peptides do not interfere with the normal uptake of surfactant by ATII. Copyright (c) 2007 S. Karger AG, Basel.
BACKGROUND: Exogenous surfactant has been accepted worldwide as a therapy of RDS in premature and term infants. Exogenous surfactant is usually derived from lung extracts containing phospholipids and the surfactant proteins SP-B and SP-C. Synthetic peptides of SP-B and SP-C are being tested with the aim to develop a completely synthetic surfactant preparation. Nevertheless, the effects of these peptides on the endogenous surfactant metabolism remain unknown. OBJECTIVES: The effect of synthetic SP-Bpeptides on uptake of surfactant-like liposomes was investigated in alveolar cells. Native SP-B and seven SP-Bpeptides were included: monomeric and dimeric SP-B(1-25) (Cys-11 --> Ala-11), SP-B(63-78)and Ala-SP-B(63-78) (Cys-71 --> Ala-71;Cys-77 --> Ala-77)and their serine mutants. METHODS: In vitro, alveolar macrophages (AM) and alveolar type II cells (ATII) were incubated with liposomes containing SP-B or one of its peptides. In vivo, rats received intratracheally various SP-Bpeptides (SP-B/lipid ratio 1:33 w/w) incorporated in fluorescent surfactant-like liposomes. One hour after instillation, AM and ATII were isolated and cell-associated fluorescence was determined using flow cytometry. Confocal laser microscopy was performed to ensure internalization of the liposomes. RESULTS: In vitro uptake by AM or ATII was not influenced by the SP-Bpeptides. In vivo, SP-B(1-25) and Ser-SP-B(1-25) increased the uptake by AM whereas dSP-B(1-25) decreased the uptake. Neither SP-B(1-25) nor dSP-B(1-25 )affected total uptake by ATII. The overall uptake by SP-B(63-78) variants was not changed. CONCLUSIONS: Surface-active synthetic SP-Bpeptides do not interfere with the normal uptake of surfactant by ATII. Copyright (c) 2007 S. Karger AG, Basel.
Authors: Petra Khan; Kleanthis Fytianos; Luca Tamò; Michael Roth; Michael Tamm; Thomas Geiser; Amiq Gazdhar; Katrin E Hostettler Journal: Respir Res Date: 2018-10-19