We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Pulmonary surfactant protein A-induced changes in the molecular conformation of bacterial deep-rough LPS lead to reduced activity on human macrophages.
- Authors
Keese, Susanne P; Brandenburg, Klaus; Roessle, Manfred; Schromm, Andra B
- 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 νasPO2-, 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.
- Subjects
PULMONARY surfactant-associated protein A; MOLECULAR conformation; BACTERIAL proteins; LIPOPOLYSACCHARIDES; MACROPHAGES; ANTI-inflammatory agents
- Publication
Innate Immunity, 2014, Vol 20, Issue 8, p787
- ISSN
1753-4259
- Publication type
Article
- DOI
10.1177/1753425913506269