Structural Changes of Surfactant Protein A Induced by Cations Reorient the Protein on Lipid Bilayers

Palaniyar, Nades; Ridsdale, Ross; Holterman, Chet E.; Inchley, Kevin; Possmayer, Fred; Harauz, George

doi:10.1006/jsbi.1998.4004

Cited by 43 publications

(41 citation statements)

References 49 publications

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“…Normal levels of ionized calcium in the blood are ϳ1.4 mM, which is similar to the concentration used in these degradation assays, but calcium levels have been known to decrease in intensive care patients and in sepsis conditions (51,52). Despite reports that the binding of calcium to SP-A causes a conformational change of the octadecamer and aggregation in vitro (53,54), the degradation of NhSP-A by Der p 1 and Der f 1 was not significantly altered in the absence of calcium, suggesting that the cleavage sites may be far away from the calcium-binding sites.…”

Section: Discussionmentioning

confidence: 78%

Major House Dust Mite Allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 Degrade and Inactivate Lung Surfactant Proteins A and D

Deb

Shakib

Reid

et al. 2007

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 78%

Major House Dust Mite Allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 Degrade and Inactivate Lung Surfactant Proteins A and D

Deb

Shakib

Reid

et al. 2007

Journal of Biological Chemistry

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“…The inhibition of degradation by the three metal ions tested is probably due to effects on the lectin domains of SP-A and SP-D rather than a direct effect on the enzyme, since the proteolytic activity of P. aeruginosa elastase is poorly inhibited by calcium, magnesium, and manganese (1 mM) in vitro (29). It has been shown that binding of calcium to SP-A causes a conformational change of the octadecamer (38). Furthermore, calcium induces a conformational change and aggregation of SP-A in vitro, which may alter availability of the protein for degradation (26).…”

Section: Degradation Of Rat Bal Results In the Production Of A 35-kdamentioning

confidence: 99%

Degradation of Pulmonary Surfactant Protein D by Pseudomonas aeruginosa Elastase Abrogates Innate Immune Function

Alcorn

Wright

2004

Journal of Biological Chemistry

110

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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)1 is one of the four surfactant proteins that is synthesized by alveolar type II epithelial cells as a component of the lipoprotein complex known as pulmonary surfactant. Although SP-D has not been shown to participate in the surface tension-reducing properties of surfactant, it has been demonstrated to participate in the host defense functions of surfactant (1). SP-D as well as SP-A belong to the collectin family of proteins, named for their N-terminal collagen region and Cterminal lectin domain. Intact SP-D consists of four trimers, which interact in their N-terminal region to form a cruciform structure (2). The collectins are pattern recognition molecules that bind, in a calcium-dependent manner, to non-self oligosaccharides presented on the surface of many bacteria and viruses. (9).Pseudomonas aeruginosa is a Gram-negative bacterium that is the predominant cause of morbidity and mortality in patients with cystic fibrosis (CF) (10). P. aeruginosa infections are characterized by a mucoid biofilm consisting mainly of secreted oligosaccharides. The lipopolysaccharide expressed by mucoid P. aeruginosa is of the rough phenotype and is less cytotoxic than that of other Gram-negative bacteria (11). Virulence is induced by P. aeruginosa via secretion of several enzymes, the most cytotoxic of which is exotoxin A, which directly inhibits protein synthesis (12). In addition to this toxin, P. aeruginosa secretes several proteases including elastase (Las B), protease IV, Las A protease, and alkaline protease (13,14).Surfactant protein composition is altered in cystic fibrosis patients. Several reports have shown that whereas phospholipids levels are largely unchanged, the levels of both intact . Surfactant protein levels have also been shown to be altered in a rat model of P. aeruginosa infection, although SP-D levels were not measured (18). We have previously shown P. aeruginosa elastase degrades both SP-A and SP-D and that SP-A degradation fragments are present in the bronchoalveolar lavage (BAL) of cystic fibrosis patients after lung transplant (19). Detectable levels of P. aeruginosa elastase have been found in the BAL and serum of CF patients (20). Furthermore, histologic studies have detected abnormal elastin fibers in lung alveoli of CF patients on autopsy (21), and P. aeruginosa elastase activity was detectable in sputum samples. These data suggest that SP-D is probably cleaved by elastase in vivo during the progression of CF.We propose that P. aeruginosa elastase cleaves SP-D to a stable 35-kDa fragment, which has impaired immune regulatory function. To test this hypothesis, we purified both P. aeruginosa elastase by ion exchange chromatography and its 35-kDa SP-D cleavage product by gel filtration chromatogra-

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“…Three amphipathic ␣-helical neck domains (9) assemble as coiledcoil bundles and hold together three globular carbohydrate recognition domains (CRDs) (9 -11). The trimeric subunits of the MBL further associate into high order oligomers consisting of two to six units (12) resembling a "bouquet of tulips," similar to that of the lung-restricted collectin, surfactant-associated protein A (SP-A) (13), and a noncollectin, complement protein C1q (14). Although the trimeric subunits of the collectins have limited affinity (micromolar) for lipid (15,16) and several carbohydrate targets (17,18), their oligomeric assembly provides a high avidity (7,19,20) so that these proteins bind to ligands selectively and with high affinity (nanomolar to picomolar).…”

mentioning

confidence: 99%

Mannose-Binding Lectin Recognizes Peptidoglycan via the N-Acetyl Glucosamine Moiety, and Inhibits Ligand-Induced Proinflammatory Effect and Promotes Chemokine Production by Macrophages

Nadesalingam

Dodds

Reid

et al. 2005

The Journal of Immunology

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Peptidoglycan (PGN) is the major cell wall component (90%, w/w) of Gram-positive bacteria and consists of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) disaccharide repeating arrays that are cross-linked by short peptides. We hypothesized that PGN is a ligand for pathogen-associated pattern-recognition proteins. Mannose-binding lectin (MBL) and serum amyloid component P are two carbohydrate-binding innate immune proteins present in the blood. In this study we show that human MBL, but not serum amyloid component P, binds significantly to PGN via its C-type lectin domains, and that the interaction can be more effectively competed by GlcNAc than by MurNAc. Surface plasmon resonance analyses show that native MBL binds immobilized PGN with high avidity. Competition experiments also show that both native MBL and MBL(n/CRD), a 48-kDa recombinant trimeric fragment of MBL containing neck and carbohydrate recognition domains, have higher affinity for GlcNAc than for MurNAc. Protein arrays and ELISA show that PGN increases the secretion of TNF-α, IL-8, IL-10, MCP-2, and RANTES from PMA-stimulated human monocytic U937 cells. Interestingly, the presence of MBL together with PGN increases the production of IL-8 and RANTES, but reduces that of TNF-α. Our results indicate that Gram-positive bacterial is a biologically relevant ligand for MBL, and that the collectin preferentially binds to the GlcNAc moiety of the PGN via its C-type lectin domains. MBL inhibits PGN-induced production of proinflammatory cytokines while enhancing the production of chemokines by macrophages, which suggests that MBL may down-regulate macrophage-mediated inflammation while enhancing phagocyte recruitment.

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Structural Changes of Surfactant Protein A Induced by Cations Reorient the Protein on Lipid Bilayers

Cited by 43 publications

References 49 publications

Major House Dust Mite Allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 Degrade and Inactivate Lung Surfactant Proteins A and D

Major House Dust Mite Allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 Degrade and Inactivate Lung Surfactant Proteins A and D

Degradation of Pulmonary Surfactant Protein D by Pseudomonas aeruginosa Elastase Abrogates Innate Immune Function

Mannose-Binding Lectin Recognizes Peptidoglycan via the N-Acetyl Glucosamine Moiety, and Inhibits Ligand-Induced Proinflammatory Effect and Promotes Chemokine Production by Macrophages

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