A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D

Rikke Leth-Larsen, Peter Garred, Henriette Jensenius, Joseph Meschi, Kevan Hartshorn, Jens Madsen, Ida Tornoe, Hans O. Madsen, Grith Sørensen, Erika Crouch, Uffe Holmskov

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Abstract

Surfactant protein D (SP-D) plays important roles in the host defense against infectious microorganisms and in regulating the innate immune response to a variety of pathogen-associated molecular pattern. SP-D is mainly expressed by type II cells of the lung, but SP-D is generally found on epithelial surfaces and in serum. Genotyping for three single-nucleotide variations altering amino acids in the mature protein in codon 11 (Met11Thr), 160 (Ala 160Thr), and 270 (Ser270Thr) of the SP-D gene was performed and related to the SP-D levels in serum. Individuals with the Thr/Thr11-encoding genotype had significantly lower SP-D serum levels than individuals with the Met/Met11 genotype. Gel filtration chromatography revealed two distinct m.w. peaks with SP-D immunoreactivity in serum from Met/Met11-encoding genotypes. In contrast, Thr/Thr 11 genotypes lacked the highest m.w. form. A similar SP-D size distribution was found for recombinant Met11 and Thr11 expressed in human embryonic kidney cells. Atomic force microscopy of purified SP-D showed that components eluting in the position of the high m.w. peak consist of multimers, dodecamers, and monomers of subunits, whereas the second peak exclusively contains monomers. SP-D from both peaks bound to mannan-coated ELISA plates. SP-D from the high m.w. peak bound preferentially to intact influenza A virus and Gram-positive and Gram-negative bacteria, whereas the monomeric species preferentially bound to isolated LPS. Our data strongly suggest that polymorphic variation in the N-terminal domain of the SP-D molecule influences oligomerization, function, and the concentration of the molecule in serum.

Original languageEnglish
Pages (from-to)1532-1538
Number of pages7
JournalJournal of Immunology
Volume174
Issue number3
DOIs
StatePublished - Feb 1 2005

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    Leth-Larsen, R., Garred, P., Jensenius, H., Meschi, J., Hartshorn, K., Madsen, J., Tornoe, I., Madsen, H. O., Sørensen, G., Crouch, E., & Holmskov, U. (2005). A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D. Journal of Immunology, 174(3), 1532-1538. https://doi.org/10.4049/jimmunol.174.3.1532