title: Pulmonary surfactant protein A-induced changes in the molecular conformation of bacterial deep-rough LPS lead to reduced activity on human macrophages.
abstract: The lung is constantly exposed to immune stimulation by LPS from inhaled microorganisms. A primary mechanism to maintain immune homeostasis is based on anti-inflammatory regulation by surfactant protein A (SP-A), a secreted component of lung innate immunity. The architecture of LPS aggregates is strongly associated with biological activity. We therefore investigated whether SP-A affects the physico-chemical properties of LPS. Determination of the three-dimensional aggregate structure of LPS by small-angle X-ray scattering demonstrated that SP-A induced the formation of multi-lamellar aggregate structures. Determination of the acyl-chain-fluidity of LPS aggregates by Fourier transform infrared (FTIR) spectroscopy showed that the phase transition temperature of LPS was reduced in the presence of SP-A. The phosphate groups at the diglucosamine backbone of LPS represent important functional groups for the bioactivity of LPS. FTIR analysis revealed changes in the vibrational bands νas PO-(2), indicating an interaction of SP-A with the 1-phosphate, but not with the 4'-phosphate. The physico-chemical changes induced by SP-A were associated with up to 90% reduction in LPS-induced TNF-α-production by human macrophages. In conclusion, our data demonstrate that the SP-A/LPS interaction induces conformational changes in LPS aggregates leading to biologically less active structures, thereby providing a new molecular mechanism of immune modulation by SP-A.
authors.affiliation: Division of Immunobiophysics, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
authors.forename: Susanne P
authors.initials: SP
authors.lastname: Keese
authors.affiliation: Division of Biophysics, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
authors.affiliation: European Molecular Biology Laboratory c/o DESY, Hamburg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Roessle
authors.affiliation: Division of Immunobiophysics, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany aschromm@fz-borstel.de.
authors.forename: Andra B
authors.initials: AB
authors.lastname: Schromm
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects*; D008968:Molecular Conformation / Q000187:drug effects; D011487:Protein Conformation; D037662:Pulmonary Surfactant-Associated Protein A / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D037662:Pulmonary Surfactant-Associated Protein A; D014409:Tumor Necrosis Factor-alpha
keywords: Lipopolysaccharide; aggregate structure; infrared spectroscopy; macrophage activation; membrane fluidity; surfactant protein