title: Effects of lipid interactions on model vesicle engulfment by alveolar macrophages.
abstract: The engulfment function of macrophages relies on complex molecular interactions involving both lipids and proteins. In particular, the clearance of apoptotic bodies (efferocytosis) is enabled by externalization on the cell target of phosphatidylserine lipids, which activate receptors on macrophages, suggesting that (local) specific lipid-protein interactions are required at least for the initiation of efferocytosis. However, in addition to apoptotic cells, macrophages can engulf foreign bodies that vary substantially in size from a few nanometers to microns, suggesting that nonspecific interactions over a wide range of length scales could be relevant. Here, we use model lipid membranes (made of phosphatidylcholine, phosphatidylserine, and ceramide) and rat alveolar macrophages to show how lipid bilayer properties probed by small-angle x-ray scattering and solid-state (2)H NMR correlate with engulfment rates measured by flow cytometry. We find that engulfment of protein-free model lipid vesicles is promoted by the presence of phosphatidylserine lipids but inhibited by ceramide, in accord with a previous study of apoptotic cells. We conclude that the roles of phosphatidylserine and ceramide in phagocytosis is based, at least in part, on lipid-mediated modification of membrane physical properties, including interactions at large length scales as well as local lipid ordering and possible domain formation.
authors: Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, Indiana; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors: Matthew J
authors: MJ
authors: Justice
authors: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors: Daniela N
authors: DN
authors: Petrusca
authors: Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, Indiana; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors: Adriana L
authors: AL
authors: Rogozea
authors: Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, Indiana.
authors: Justin A
authors: JA
authors: Williams
authors: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors: Kelly S
authors: KS
authors: Schweitzer
authors: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Medicine, Richard L. Roudebush Veterans' Affairs Medical Center, Indianapolis, Indiana.
authors: Irina
authors: I
authors: Petrache
authors: Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, Indiana.
authors: Stephen R
authors: SR
authors: Wassall
authors: Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, Indiana. Electronic address: hpetrach@iupui.edu.
authors: Horia I
authors: HI
authors: Petrache
mesh_terms: D000818:Animals; D002460:Cell Line; D002518:Ceramides / Q000737:chemistry / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D010587:Phagocytosis; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats
chemical_list: D002518:Ceramides; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010718:Phosphatidylserines