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Innate Immun. 2014 Nov;20(8):787-98. doi: 10.1177/1753425913506269. Epub 2013 Oct 11.

Pulmonary surfactant protein A-induced changes in the molecular conformation of bacterial deep-rough LPS lead to reduced activity on human macrophages.

Author information

1
Division of Immunobiophysics, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
2
Division of Biophysics, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
3
European Molecular Biology Laboratory c/o DESY, Hamburg, Germany.
4
Division of Immunobiophysics, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany aschromm@fz-borstel.de.

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.

KEYWORDS:

Lipopolysaccharide; aggregate structure; infrared spectroscopy; macrophage activation; membrane fluidity; surfactant protein

PMID:
24122298
DOI:
10.1177/1753425913506269
[Indexed for MEDLINE]

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