scholarly journals Contributions of the N- and C-Terminal Domains of Surfactant Protein D to the Binding, Aggregation, and Phagocytic Uptake of Bacteria

2002 ◽  
Vol 70 (11) ◽  
pp. 6129-6139 ◽  
Author(s):  
Kevan L. Hartshorn ◽  
Mitchell R. White ◽  
Erika C. Crouch
Keyword(s):  
Influenza Virus ◽  
Surfactant Protein ◽  
Binding Activity ◽  
Surfactant Protein D ◽  
Wild Type ◽  
Carbohydrate Recognition ◽  
Gram Positive Bacteria ◽  
Viral Binding ◽  
Bacterial Binding ◽  
Carbohydrate Recognition Domains

ABSTRACT Collectins play important roles in host defense against infectious microorganisms. We now demonstrate that the serum collectins mannose-binding lectin (MBL) and conglutinin have less ability to bind to, aggregate, and enhance neutrophil uptake of several strains of gram-negative and gram-positive bacteria than pulmonary surfactant protein D (SP-D). Collectins are composed of four major structural domains (i.e., N-terminal, collagen, and neck and carbohydrate recognition domains). To determine which domains of SP-D are responsible for its greater bacterial binding or aggregating activity, activities of chimeric collectins containing the N-terminal and collagen domains of SP-D coupled to the neck recognition domains and carbohydrate recognition domains (CRD) of MBL or conglutinin (SP-D/Congneck+CRD and SP-D/MBLneck+CRD) were tested. The SP-D/Congneck+CRD and SP-D/MBLneck+CRD chimeras bound to and aggregated the bacteria more strongly than did wild-type MBL or conglutinin. SP-D/MBLneck+CRD also enhanced neutrophil uptake of bacteria more so than MBL. Hence, the SP-D N-terminal and/or collagen domains contribute to the enhanced bacterial binding and aggregating activities of SP-D. In prior studies, SP-D/Congneck+CRD and SP-D/MBLneck+CRD had increased ability to bind to influenza virus compared not only with that of conglutinin or MBL but with that of wild-type SP-D as well. In contrast, the chimeras had either reduced or unchanged ability to bind to or aggregate bacteria compared to that of wild-type SP-D. Hence, although replacement of the neck recognition domains and CRDs of SP-D with those of MBL and conglutinin conferred increased viral binding activity, it did not favorably affect bacterial binding activity, suggesting that requirements for optimal collectin binding to influenza virus and bacteria differ.

scholarly journals The α-helical neck region of human lung surfactant protein D is essential for the binding of the carbohydrate recognition domains to lipopolysaccharides and phospholipids

1996 ◽  
Vol 318 (2) ◽  
pp. 505-511 ◽  
Author(s):  
Uday KISHORE ◽  
Jiu-Yao WANG ◽  
Hans-Jürgen HOPPE ◽  
Kenneth B. M. REID
Keyword(s):  
Human Lung ◽  
Lung Surfactant ◽  
Neck Region ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Carbohydrate Binding ◽  
Carbohydrate Recognition ◽  
E Coli ◽  
Carbohydrate Recognition Domains ◽  
Lung Surfactant Protein

We have expressed the carbohydrate recognition domains (CRDs) of human lung surfactant protein D (SP-D) in Escherichia coli as a trimeric structure held together by the α-helical neck region of the molecule. The DNA sequence coding for the neck-region peptide and the CRD of SP-D was subcloned and expressed as a fusion protein containing the E. coli maltose binding protein (MBP). After removal of the MBP, the recombinant structure, containing three CRDs of SP-D, was found to be comparable to native SP-D in terms of carbohydrate binding specificity, the binding to lipopolysaccharides (LPSs) of Gram-negative bacteria, and interaction with phospholipids. The CRD of SP-D, without the neck region peptide, was also expressed and shown to behave as a monomer that showed a very weak affinity for maltose-agarose, LPSs and phospholipids. The α-helical neck region on its own showed affinity for phospholipids and thus might contribute to the binding of SP-D to these structures. However, the possibility that hydrophobic patches, which are exposed only in the isolated neck region and not in the intact SP-D, plays a role in neck region–phospholipid interaction, cannot be excluded. The results confirm the importance of the neck region as a trimerizing agent in bringing together three CRDs and suggest that multivalency is important in the strong binding of SP-D to carbohydrate targets.

Genomic analysis of C-type lectins

2002 ◽  
Vol 69 ◽  
pp. 59-72 ◽  
Author(s):  
Kurt Drickamer ◽  
Andrew J. Fadden
Keyword(s):  
Biological Effects ◽  
Cell Signalling ◽  
Genomic Analysis ◽  
Binding Activity ◽  
Immunoglobulin Superfamily ◽  
Carbohydrate Binding ◽  
Carbohydrate Recognition ◽  
Calcium Dependent ◽  
Binding Domains ◽  
Carbohydrate Recognition Domains

Many biological effects of complex carbohydrates are mediated by lectins that contain discrete carbohydrate-recognition domains. At least seven structurally distinct families of carbohydrate-recognition domains are found in lectins that are involved in intracellular trafficking, cell adhesion, cell–cell signalling, glycoprotein turnover and innate immunity. Genome-wide analysis of potential carbohydrate-binding domains is now possible. Two classes of intracellular lectins involved in glycoprotein trafficking are present in yeast, model invertebrates and vertebrates, and two other classes are present in vertebrates only. At the cell surface, calcium-dependent (C-type) lectins and galectins are found in model invertebrates and vertebrates, but not in yeast; immunoglobulin superfamily (I-type) lectins are only found in vertebrates. The evolutionary appearance of different classes of sugar-binding protein modules parallels a development towards more complex oligosaccharides that provide increased opportunities for specific recognition phenomena. An overall picture of the lectins present in humans can now be proposed. Based on our knowledge of the structures of several of the C-type carbohydrate-recognition domains, it is possible to suggest ligand-binding activity that may be associated with novel C-type lectin-like domains identified in a systematic screen of the human genome. Further analysis of the sequences of proteins containing these domains can be used as a basis for proposing potential biological functions.

Human surfactant protein D: SP-D contains a C-type lectin carbohydrate recognition domain

1991 ◽  
Vol 290 (1) ◽  
pp. 116-126 ◽  
Author(s):  
Kevin Rust ◽  
Leonard Grosso ◽  
Vivian Zhang ◽  
Donald Chang ◽  
Anders Persson ◽  
...  
Keyword(s):  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Carbohydrate Recognition Domain ◽  
Carbohydrate Recognition

scholarly journals Implication of Antigenic Conversion of Helicobacter pylori Lipopolysaccharides That Involve Interaction with Surfactant Protein D

2012 ◽  
Vol 80 (8) ◽  
pp. 2956-2962 ◽  
Author(s):  
Shin-ichi Yokota ◽  
Ken-ichi Amano ◽  
Chiaki Nishitani ◽  
Shigeru Ariki ◽  
Yoshio Kuroki ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Biological Activities ◽  
Surfactant Protein ◽  
Binding Activity ◽  
Surfactant Protein D ◽  
Dependent Manner ◽  
Antigenic Epitope ◽  
Binding Assays ◽  
Content Type ◽  
Gastric Cancer Patients

ABSTRACTWe propose two antigenic types ofHelicobacter pylorilipopolysaccharides (LPS): highly antigenic epitope-carrying LPS (HA-LPS) and weakly antigenic epitope-carrying LPS (WA-LPS) based on human serum reactivity. Strains carrying WA-LPS are highly prevalent in isolates from gastric cancer patients. WA-LPS exhibits more potent biological activities compared to HA-LPS, namely, upregulation of Toll-like receptor 4 (TLR4) expression and induction of enhanced epithelial cell proliferation. The results of competitive binding assays using monosaccharides and methylglycosides, as well as binding assays using glycosidase-treated LPS, suggested that β-linkedN-acetyl-d-glucosamine and β-linkedd-galactose residues largely contributed to the highly antigenic epitope and the weakly antigenic epitope, respectively. WA-LPS exhibited greater binding activity to surfactant protein D (SP-D) in a Ca2+-dependent manner, and this interaction was inhibited by methyl-β-d-galactoside. The biological activities of WA-LPS were markedly enhanced by the addition of SP-D. Lines of evidence suggested that removal of β-N-acetyl-d-glucosamine residue, which comprises the highly antigenic epitope, results in exposure of the weakly antigenic epitope. The weakly antigenic epitope interacted preferentially with SP-D, and SP-D enhanced the biological activity of WA-LPS.

Contractile Changes in the Vasculature After Subchronic Smoking: A Comparison Between Wild Type and Surfactant Protein D Knock-Out Mice

2015 ◽  
Vol 18 (5) ◽  
pp. 642-646 ◽  
Author(s):  
Kristian Agmund Haanes ◽  
Lars Schack Kruse ◽  
Helle Wulf-Johansson ◽  
Christian Christensen Stottrup ◽  
Grith Lykke Sorensen ◽  
...  
Keyword(s):  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Wild Type ◽  
Knock Out ◽  
Knock Out Mice

scholarly journals Surfactant Protein D Increases Phagocytosis of Hypocapsular Cryptococcus neoformans by Murine Macrophages and Enhances Fungal Survival

2009 ◽  
Vol 77 (7) ◽  
pp. 2783-2794 ◽  
Author(s):  
Scarlett Geunes-Boyer ◽  
Timothy N. Oliver ◽  
Guilhem Janbon ◽  
Jennifer K. Lodge ◽  
Joseph Heitman ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Defense Mechanisms ◽  
Protein A ◽  
Surfactant Protein ◽  
Immune Defense ◽  
Surfactant Protein D ◽  
Wild Type ◽  
Phagocytic Cells

ABSTRACT Cryptococcus neoformans is a facultative intracellular opportunistic pathogen and the leading cause of fungal meningitis in humans. In the absence of a protective cellular immune response, the inhalation of C. neoformans cells or spores results in pulmonary infection. C. neoformans cells produce a polysaccharide capsule composed predominantly of glucuronoxylomannan, which constitutes approximately 90% of the capsular material. In the lungs, surfactant protein A (SP-A) and SP-D contribute to immune defense by facilitating the aggregation, uptake, and killing of many microorganisms by phagocytic cells. We hypothesized that SP-D plays a role in C. neoformans pathogenesis by binding to and enhancing the phagocytosis of the yeast. Here, the abilities of SP-D to bind to and facilitate the phagocytosis and survival of the wild-type encapsulated strain H99 and the cap59Δ mutant hypocapsular strain are assessed. SP-D binding to cap59Δ mutant cells was approximately sixfold greater than binding to wild-type cells. SP-D enhanced the phagocytosis of cap59Δ cells by approximately fourfold in vitro. To investigate SP-D binding in vivo, SP-D−/− mice were intranasally inoculated with Alexa Fluor 488-labeled cap59Δ or H99 cells. By confocal microscopy, a greater number of phagocytosed C. neoformans cells in wild-type mice than in SP-D−/− mice was observed, consistent with in vitro data. Interestingly, SP-D protected C. neoformans cells against macrophage-mediated defense mechanisms in vitro, as demonstrated by an analysis of fungal viability using a CFU assay. These findings provide evidence that C. neoformans subverts host defense mechanisms involving surfactant, establishing a novel virulence paradigm that may be targeted for therapy.

scholarly journals Influenza Virus Hemagglutinins H2, H5, H6, and H11 Are Not Targets of Pulmonary Surfactant Protein D: N-Glycan Subtypes in Host-Pathogen Interactions

2019 ◽  
Vol 94 (5) ◽  
Author(s):  
Lisa M. Parsons ◽  
Yanming An ◽  
Li Qi ◽  
Mitchell R. White ◽  
Roosmarijn van der Woude ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Pulmonary Surfactant ◽  
Three Dimensional ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Human Populations ◽  
Head Region ◽  
High Mannose ◽  
Pulmonary Surfactant Protein ◽  
High Mannose Glycan

ABSTRACT Seasonal influenza carrying key hemagglutinin (HA) head region glycosylation sites can be removed from the lung by pulmonary surfactant protein D (SP-D). Little is known about HA head glycosylation of low-pathogenicity avian influenza virus (LPAIV) subtypes. These can pose a pandemic threat through reassortment and emergence in human populations. Since the presence of head region high-mannose glycosites dictates SP-D activity, the ability to predict these glycosite glycan subtypes may be of value. Here, we investigate the activities of two recombinant human SP-D forms against representative LPAIV strains, including H2N1, H5N1, H6N1, H11N9, an avian H3N8, and a human seasonal H3N2 subtype. Using mass spectrometry, we determined the glycan subclasses and heterogeneities at each head glycosylation site. Sequence alignment and molecular structure analysis of the HAs were performed for LPAIV strains in comparison to seasonal H3N2 and avian H3N8. Intramolecular contacts were determined between the protein backbone and glycosite glycan based on available three-dimensional structure data. We found that glycosite “N165” (H3 numbering) is occupied by high-mannose glycans in H3 HA but by complex glycans in all LPAIV HAs. SP-D was not active on LPAIV but was on H3 HAs. Since SP-D affinity for influenza HA depends on the presence of high-mannose glycan on the head region, our data demonstrate that SP-D may not protect against virus containing these HA subtypes. Our results also demonstrate that glycan subtype can be predicted at some glycosites based on sequence comparisons and three-dimensional structural analysis. IMPORTANCE Low-pathogenicity avian influenza virus (LPAIV) subtypes can reassort with circulating human strains and pandemic viruses can emerge in human populations, as was seen in the 1957 pandemic, in which an H2 virus reassorted with the circulating H1N1 to create a novel H2N2 genotype. Lung surfactant protein D (SP-D), a key factor in first-line innate immunity defense, removes influenza type A virus (IAV) through interaction with hemagglutinin (HA) head region high-mannose glycan(s). While it is known that both H1 and H3 HAs have one or more key high-mannose glycosites in the head region, little is known about similar glycosylation of LPAIV strains H2N1, H5N1, H6N1, or H11N9, which may pose future health risks. Here, we demonstrate that the hemagglutinins of LPAIV strains do not have the required high-mannose glycans and do not interact with SP-D, and that sequence analysis can predict glycan subtype, thus predicting the presence or absence of this virulence marker.

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