Expression of Surfactant Protein D in the Human Gastric Mucosa and during Helicobacter pylori Infection

ABSTRACT Helicobacter pylori establishes persistent infection of gastric mucosa with diverse clinical outcomes. The innate immune molecule surfactant protein D (SP-D) binds selectively to microorganisms, inducing aggregation and phagocytosis. In this study, we demonstrated the expression of SP-D in gastric mucosa by reverse transcription-PCR and immuohistochemical analysis. SP-D is present at the luminal surface and within the gastric pits, with maximal expression at the surface. Levels of expression are significantly increased in H. pylori-associated gastritis compared to those in the normal mucosa. Immunofluorescence microscopy was used to demonstrate binding and agglutination of H. pylori by SP-D in a lectin-specific manner. These activities resulted in a 50% reduction in the motility of H. pylori, as judged on the basis of curvilinear velocity measured by using a Hobson BacTracker. Lipopolysaccharides extracted from three H. pylori strains were shown to bind SP-D in a concentration-dependent manner, and there was marked variation in the avidity of binding among the strains. SP-D may therefore play a significant role in the innate immune response to H. pylori infection.

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Variations in Helicobacter pylori Lipopolysaccharide To Evade the Innate Immune Component Surfactant Protein D

Infection and Immunity ◽

10.1128/iai.73.11.7677-7686.2005 ◽

2005 ◽

Vol 73 (11) ◽

pp. 7677-7686 ◽

Cited By ~ 38

Author(s):

Wafa Khamri ◽

Anthony P. Moran ◽

Mulugeta L. Worku ◽

Q. Najma Karim ◽

Marjorie M. Walker ◽

...

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Phase Variation ◽

Surfactant Protein ◽

Clinical Isolates ◽

Surfactant Protein D ◽

Human Gastric Mucosa ◽

H Pylori

ABSTRACT Helicobacter pylori is a common and persistent human pathogen of the gastric mucosa. Surfactant protein D (SP-D), a component of innate immunity, is expressed in the human gastric mucosa and is capable of aggregating H. pylori. Wide variation in the SP-D binding affinity to H. pylori has been observed in clinical isolates and laboratory-adapted strains. The aim of this study was to reveal potential mechanisms responsible for evading SP-D binding and establishing persistent infection. An escape variant, J178V, was generated in vitro, and the lipopolysaccharide (LPS) structure of the variant was compared to that of the parental strain, J178. The genetic basis for structural variation was explored by sequencing LPS biosynthesis genes. SP-D binding to clinical isolates was demonstrated by fluorescence-activated cell sorter analyses. Here, we show that H. pylori evades SP-D binding through phase variation in lipopolysaccharide. This phenomenon is linked to changes in the fucosylation of the O chain, which was concomitant with slipped-strand mispairing in a poly(C) tract of the fucosyltransferase A (fucT1) gene. SP-D binding organisms are predominant in mucus in vivo (P = 0.02), suggesting that SP-D facilitates physical elimination. Phase variation to evade SP-D contributes to the persistence of this common gastric pathogen.

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Sex and SP-A2 Dependent NAD(H) Redox Alterations in Mouse Alveolar Macrophages in Response to Ozone Exposure: Potential Implications for COVID-19

Antioxidants ◽

10.3390/antiox9100915 ◽

2020 ◽

Vol 9 (10) ◽

pp. 915

Author(s):

He N. Xu ◽

Zhenwu Lin ◽

Chintan K. Gandhi ◽

Shaili Amatya ◽

Yunhua Wang ◽

...

Keyword(s):

Alveolar Macrophages ◽

Imaging Technique ◽

Redox Balance ◽

Surfactant Protein ◽

Redox Status ◽

Innate Immune ◽

Ozone Exposure ◽

Dependent Manner ◽

Immune Molecule ◽

Air Control

Co-enzyme nicotinamide adenine dinucleotide (NAD(H)) redox plays a key role in macrophage function. Surfactant protein (SP-) A modulates the functions of alveolar macrophages (AM) and ozone (O3) exposure in the presence or absence of SP-A and reduces mouse survival in a sex-dependent manner. It is unclear whether and how NAD(H) redox status plays a role in the innate immune response in a sex-dependent manner. We investigated the NAD(H) redox status of AM from SP-A2 and SP-A knockout (KO) mice in response to O3 or filtered air (control) exposure using optical redox imaging technique. We found: (i) In SP-A2 mice, the redox alteration of AM in response to O3 showed sex-dependence with AM from males being significantly more oxidized and having a higher level of mitochondrial reactive oxygen species than females; (ii) AM from KO mice were more oxidized after O3 exposure and showed no sex differences; (iii) AM from female KO mice were more oxidized than female SP-A2 mice; and (iv) Two distinct subpopulations characterized by size and redox status were observed in a mouse AM sample. In conclusions, the NAD(H) redox balance in AM responds to O3 in a sex-dependent manner and the innate immune molecule, SP-A2, contributes to this observed sex-specific redox response.

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Innate Immune Molecule Surfactant Protein D Attenuates Sepsis-induced Acute Pancreatic Injury through Modulating Apoptosis and NF-κB-mediated Inflammation

Scientific Reports ◽

10.1038/srep17798 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 21

Author(s):

Zhiyong Liu ◽

Qiao Shi ◽

Jiao Liu ◽

Osama Abdel-Razek ◽

Yongan Xu ◽

...

Keyword(s):

Pancreatic Injury ◽

Surfactant Protein ◽

Innate Immune ◽

Surfactant Protein D ◽

Immune Molecule

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Rat surfactant protein D enhances the production of oxygen radicals by rat alveolar macrophages

Biochemical Journal ◽

10.1042/bj2860005 ◽

1992 ◽

Vol 286 (1) ◽

pp. 5-8 ◽

Cited By ~ 81

Author(s):

J F Van Iwaarden ◽

H Shimizu ◽

P H M Van Golde ◽

D R Voelker ◽

L M G Van Golde

Keyword(s):

Alveolar Macrophages ◽

Oxygen Radicals ◽

Protein A ◽

Surfactant Protein ◽

Surfactant Protein A ◽

Surfactant Protein D ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Oxygen Radical Production ◽

Stimulation Of

Rat surfactant protein D (SP-D) was shown to enhance the production of oxygen radicals by rat alveolar macrophages. This enhancement, which was determined by a lucigenin-dependent chemiluminescence assay, was maximal after 18 min at an SP-D concentration of 0.2 micrograms/ml. Surfactant lipids did not influence the stimulation of alveolar macrophages by SP-D, whereas the oxygen-radical production of these cells induced by surfactant protein A was inhibited by the lipids in a concentration-dependent manner.

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Surfactant protein D (SP-D) counteracts the inhibitory effect of surfactant protein A (SP-A) on phospholipid secretion by alveolar type II cells. Interaction of native SP-D with SP-A

Biochemical Journal ◽

10.1042/bj2790115 ◽

1991 ◽

Vol 279 (1) ◽

pp. 115-119 ◽

Cited By ~ 22

Author(s):

Y Kuroki ◽

M Shiratori ◽

Y Murata ◽

T Akino

Keyword(s):

Surfactant Protein ◽

Inhibitory Effect ◽

Surfactant Protein D ◽

Alveolar Type ◽

Type Ii Cells ◽

Dependent Manner ◽

Type Ii ◽

Alveolar Type Ii Cells ◽

Concentration Dependent Manner ◽

Surfactant Secretion

The surfactant proteins SP-A and SP-D were obtained from rats given intratracheal instillation of silica. SP-D was isolated from the 33,000 g supernatant of rat bronchoalveolar lavage fluids, and we examined whether SP-D affects surfactant secretion by alveolar type II cells. Native SP-D affected neither basal secretion nor stimulated secretion by type II cells. However, native SP-D counteracted the inhibitory effect of SP-A on surfactant secretion in a concentration-dependent manner; however, SP-D failed to counteract the inhibitory effect of concanavalin A. The activity of SP-D was unaffected by inclusion of excess methyl alpha-mannoside. Excess native SP-D competed with 125I-SP-A for high-affinity binding to type II cells. Heat treatment of SP-D and antibody against SP-D both decreased SP-D activity. Butanol extraction of native SP-D was most effective at destroying SP-D activity and attenuated the ability of the protein to compete with labelled SP-A for binding to type II cells. The butanol-soluble fraction of SP-D possessed the ability to alter the inhibitory effect of SP-A to the same extent as native SP-D. Direct binding of 125I-SP-A on nitrocellulose sheets demonstrated that SP-A could bind native SP-D, but not butanol-extracted SP-D. We conclude that native SP-D alters SP-A activity in type II cells through interaction with it via SP-D-associated lipids.

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Surfactant protein D enhances bacterial antigen presentation by bone marrow-derived dendritic cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.281.6.l1453 ◽

2001 ◽

Vol 281 (6) ◽

pp. L1453-L1463 ◽

Cited By ~ 67

Author(s):

Karen G. Brinker ◽

Emily Martin ◽

Paul Borron ◽

Elahe Mostaghel ◽

Carolyn Doyle ◽

...

Keyword(s):

Bone Marrow ◽

Immune Response ◽

Dendritic Cells ◽

Antigen Presentation ◽

Surfactant Protein ◽

Innate Immune ◽

Surfactant Protein D ◽

Mouse Bone Marrow ◽

Bacterial Antigen ◽

Dependent Manner

Surfactant protein (SP) D functions as a soluble pattern recognition molecule to mediate the clearance of pathogens by phagocytes in the innate immune response. We hypothesize that SP-D may also interact with dendritic cells, the most potent antigen presenting cell, to enhance uptake and presentation of bacterial antigens. Using mouse bone marrow-derived dendritic cells, we show that SP-D binds to immature dendritic cells in a dose-, carbohydrate-, and calcium-dependent manner, whereas SP-D binding to mature dendritic cells is reduced. SP-D also binds to Escherichia coli HB101 and enhances its association with dendritic cells. Additionally, SP-D enhances the antigen presentation of an ovalbumin fusion protein expressed in E. coli HB101 to ovalbumin-specific major histocompatibility complex class II T cell hybridomas. The enhancement of antigen presentation by SP-D is dose dependent and is not shared by other collectin-like proteins tested. These studies demonstrate that SP-D augments antigen presentation by dendritic cells and suggest that innate immune molecules such as SP-D may help initiate an adaptive immune response for the purpose of resolving an infection.

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Innate immune molecule surfactant protein D attenuates sepsis‐induced acute kidney injury through modulating apoptosis and NFκB‐mediated inflammation

International Wound Journal ◽

10.1111/iwj.13237 ◽

2019 ◽

Vol 17 (1) ◽

pp. 100-106 ◽

Cited By ~ 1

Author(s):

Shi‐Jun Lu ◽

Jian‐Hua Xu ◽

Zhao‐Feng He ◽

Peng Wu ◽

Chao Ning ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Surfactant Protein ◽

Innate Immune ◽

Surfactant Protein D ◽

Immune Molecule

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Toll-like receptor (TLR) 2 induced through TLR4 signaling initiated byHelicobacter pyloricooperatively amplifies iNOS induction in gastric epithelial cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00096.2007 ◽

2007 ◽

Vol 293 (5) ◽

pp. G1004-G1012 ◽

Cited By ~ 56

Author(s):

Kaname Uno ◽

Katsuaki Kato ◽

Tomoaki Atsumi ◽

Takehito Suzuki ◽

Jun Yoshitake ◽

...

Keyword(s):

Gastric Mucosa ◽

Epithelial Cells ◽

Innate Immune ◽

Human Gastric Mucosa ◽

Gastric Epithelial Cells ◽

Tlr4 Signaling ◽

Extracellular Signal ◽

Mitogen Activated Protein ◽

H Pylori ◽

Inos Induction

Cell-surface Toll-like receptors (TLRs) initiate innate immune responses, such as inducible nitric oxide synthase (iNOS) induction, to microorganisms' surface pathogens. TLR2 and TLR4 play important roles in gastric mucosa infected with Helicobacter pylori ( H. pylori), which contains lipopolysaccharide (LPS) as a pathogen. The present study investigates their physiological roles in the innate immune response of gastric epithelial cells to H. pylori-LPS. Changes in the expression of iNOS, TLR2, and TLR4, as well as downstream activation of mitogen-activated protein kinases and nuclear factor-κB (NF-κB), were analyzed in normal mouse gastric mucosal GSM06 cells following stimulation with H. pylori-LPS and interferon-γ. Specific inhibitors for mitogen-activated protein kinases, NF-κB, and small interfering RNA for TLR2 or TLR4 were employed. The immunohistochemistry of TLR2 was examined in human gastric mucosa. H. pylori-LPS stimulation induced TLR2 in GSM06 cells, but TLR4 was unchanged. TLR2 induction resulted from TLR4 signaling that propagated through extracellular signal-related kinase and NF-κB activation, as corroborated by the decline in TLR4 expression on small interfering RNA treatment and pretreatment with inhibitors. The induction of iNOS and the associated nitric oxide production in response to H. pylori-LPS stimulation were inhibited by declines in not only TLR4 but also TLR2. Increased expression of TLR2 was identified in H. pylori-infected human gastric mucosa. TLR4 signaling initiated by H. pylori-LPS and propagated via extracellular signal-regulated kinase and NF-κB activation induced TLR2 expression in gastric epithelial cells. Induced TLR2 cooperated with TLR4 to amplify iNOS induction. This positive correlation may constitute a mechanism for stimulating the innate immune response against various bacterial pathogens, including H. pylori-LPS.

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