PMID:15123664

Citation	Alcorn, JF and Wright, JR (2004) Degradation of pulmonary surfactant protein D by Pseudomonas aeruginosa elastase abrogates innate immune function. J. Biol. Chem. 279:30871-9
Abstract	The alveolar epithelium is lined by surfactant, a lipoprotein complex that both reduces surface tension and mediates several innate immune functions including bacterial aggregation, alteration of alveolar macrophage function, and regulation of bacterial clearance. Surfactant protein-D (SP-D) participates in several of these immune functions, and specifically it enhances the clearance of the pulmonary pathogen Pseudomonas aeruginosa, a common cause of morbidity and mortality in cystic fibrosis (CF) patients. P. aeruginosa secretes a variety of virulence factors including elastase, a zinc-metalloprotease, which degrades both SP-A and SP-D. Here we show that SP-D is cleaved by elastase to produce a stable 35-kDa fragment in a time-, temperature-, and dose-dependent manner. Degradation is inhibited by divalent metal cations, a metal chelator, and the elastase inhibitor, phosphoramidon. Sequencing the SP-D degradation products localized the major cleavage sites to the C-terminal lectin domain. The SP-D fragment fails to bind or aggregate bacteria that are aggregated by intact SP-D. SP-D fragment is observed when normal rat bronchoalveolar lavage (BAL) is treated with Pseudomonas aeruginosa elastase, and SP-D fragments are present in the BAL of CF lung allograft patients. These data show that degradation of SP-D occurs in the BAL environment and that degradation eliminates many normal immune functions of SP-D.
Links	PubMed Online version:10.1074/jbc.M400796200
Keywords	Amino Acid Sequence; Animals; Bacterial Proteins/chemistry; Bacterial Proteins/metabolism; Bronchoalveolar Lavage Fluid; Cations; Cell Separation; Chelating Agents/pharmacology; Chromatography, Gel; Cystic Fibrosis/metabolism; Dose-Response Relationship, Drug; Epithelium/metabolism; Flow Cytometry; Humans; Lectins/chemistry; Lung/cytology; Lung/metabolism; Lung Transplantation; Macrophages/metabolism; Metalloendopeptidases/chemistry; Metalloendopeptidases/metabolism; Molecular Sequence Data; Phagocytosis; Protein Binding; Protein Structure, Tertiary; Pulmonary Alveoli/metabolism; Pulmonary Surfactant-Associated Protein D/metabolism; Rats; Recombinant Proteins/metabolism; Salmonella typhimurium/metabolism; Temperature; Time Factors
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
PSEAE:ELAS	involved_in	GO:0052051: interaction with host via protein secreted by type II secretion system	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

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