Myeloperoxidase-dependent inactivation of surfactant protein D in vitro and in vivo

Erika C. Crouch, Tim O. Hirche, Baohai Shao, Rachel Boxio, Julien Wartelle, Rym Benabid, Barbara McDonald, Jay Heinecke, Sadis Matalon, Azzaq Belaaouaj

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Surfactant protein D (SP-D) plays diverse and important roles in innate immunity and pulmonary homeostasis. Neutrophils and myeloperoxidase (MPO) colocalized with SP-D in a murine bacterial pneumonia model of acute inflammation, suggesting that MPO-derived reactive species might alter the function of SP-D. Exposure of SP-D to the completeMPO-H2O 2-halide system caused loss of SP-D-dependent aggregating activity. Hypochlorous acid (HOCI), the major oxidant generated by MPO, caused a similar loss of aggregating activity, which was accompanied by the generation of abnormal disulfide-cross-linked oligomers. A full-length SP-D mutant lacking N-terminal cysteine residues and truncation mutants lacking the N-terminal domains were resistant to the oxidant-induced alterations in disulfide bonding. Mass spectroscopy of HOCI-treated human SP-D demonstrated several modifications, but none involved key ligand binding residues. There was detectable oxidation of cysteine 15, but no HOCl-induced cysteine modifications were observed in the C-terminal lectin domain. Together, the findings localize abnormal disulfide cross-links to the N-terminal domain. MPO-deficient mice showed decreased cross-linking of SP-D and increased SP-D-dependent aggregating activity in the pneumonia model. Thus, MPO-derived oxidants can lead to modifications of SP-D structure with associated alterations in its characteristic aggregating activity.

Original languageEnglish
Pages (from-to)16757-16770
Number of pages14
JournalJournal of Biological Chemistry
Issue number22
StatePublished - May 28 2010


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