RT Journal Article T1 The interplay of lung surfactant proteins and lipids assimilates the macrophage clearance of nanoparticles A1 Ruge, Christian A1 Schaefer, Ulrich A1 Herrmann, Jennifer A1 Kirch, Julian A1 Cañadas Benito, Olga A1 Echaide Torreguitar, Mercedes A1 Pérez Gil, Jesús A1 Casals Carro, María Jesús A1 Müller, Rolf A1 Lehr, Claus AB The peripheral lungs are a potential entrance portal for nanoparticles into the human body due to their large surface area. The fact that nanoparticles can be deposited in the alveolar region of the lungs is of interest for pulmonary drug delivery strategies and is of equal importance for toxicological considerations. Therefore, a detailed understanding of nanoparticle interaction with the structures of this largest and most sensitive part of the lungs is important for both nanomedicine and nanotoxicology. Astonishingly, there is still little known about the bio-nano interactions that occur after nanoparticle deposition in the alveoli. In this study, we compared the effects of surfactant-associated protein A (SP-A) and D (SP-D) on the clearance of magnetite nanoparticles (mNP) with either more hydrophilic (starch) or hydrophobic (phosphatidylcholine) surface modification by an alveolar macrophage (AM) cell line (MH-S) using flow cytometry and confocal microscopy. Both proteins enhanced the AM uptake of mNP compared with pristine nanoparticles; for the hydrophilic ST-mNP, this effect was strongest with SP-D, whereas for the hydrophobic PL-mNP it was most pronounced with SP-A. Using gel electrophoretic and dynamic light scattering methods, we were able to demonstrate that the observed cellular effects were related to protein adsorption and to protein-mediated interference with the colloidal stability. Next, we investigated the influence of various surfactant lipids on nanoparticle uptake by AM because lipids are the major surfactant component. Synthetic surfactant lipid and isolated native surfactant preparations significantly modulated the effects exerted by SP-A and SP-D, respectively, resulting in comparable levels of macrophage interaction for both hydrophilic and hydrophobic nanoparticles. Our findings suggest that because of the interplay of both surfactant lipids and proteins, the AM clearance of nanoparticles is essentially the same, regardless of different intrinsic surface properties. PB Public Library of Science SN 1932-6203 YR 2012 FD 2012 LK https://hdl.handle.net/20.500.14352/96634 UL https://hdl.handle.net/20.500.14352/96634 LA eng NO Ruge CA, Schaefer UF, Herrmann J, Kirch J, Cañadas O, Echaide M, Pérez-Gil J, Casals C, Müller R, Lehr CM. 2012. The interplay of lung surfactant proteins and lipids assimilates the macrophage clearance of nanoparticles. PLoS One. 2012; 7(7):e40775 NO German Research Foundation NO Instituto de Salud Carlos III NO Ministerio de Economía y Competitividad (España) DS Docta Complutense RD 9 abr 2025