scholarly journals Role of Surfactant Protein D in Experimental Otitis Media

2021 ◽  
pp. 1-14
Author(s):  
Osama Abdel-Razek ◽  
Tianyi Liu ◽  
Xinghua Chen ◽  
Qiushi Wang ◽  
Gautam Vanga ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Otitis Media ◽  
Critical Role ◽  
Surfactant Protein ◽  
Saline Control ◽  
Surfactant Protein D ◽  
Bacterial Colony ◽  
Sterile Saline ◽  
Mucosal Thickness

Surfactant protein D (SP-D) is a C-type collectin and plays an important role in innate immunity and homeostasis in the lung. This study studied SP-D role in the nontypeable <i>Haemophilus influenzae</i> (NTHi)-induced otitis media (OM) mouse model. Wild-type C57BL/6 (WT) and SP-D knockout (KO) mice were used in this study. Mice were injected in the middle ear (ME) with 5 μL of NTHi bacterial solution (3.5 × 10<sup>5</sup> CFU/ear) or with the same volume of sterile saline (control). Mice were sacrificed at 3 time points, days 1, 3, and 7, after treatment. We found SP-D expression in the Eustachian tube (ET) and ME mucosa of WT mice but not in SP-D KO mice. After infection, SP-D KO mice showed more intense inflammatory changes evidenced by the increased mucosal thickness and inflammatory cell infiltration in the ME and ET compared to WT mice (<i>p</i> &#x3c; 0.05). Increased bacterial colony-forming units and cytokine (IL-6 and IL-1β) levels in the ear washing fluid of infected SP-D KO mice were compared to infected WT mice. Molecular analysis revealed higher levels of NF-κB and NLRP3 activation in infected SP-D KO compared to WT mice (<i>p</i> &#x3c; 0.05). In vitro studies demonstrated that SP-D significantly induced NTHi bacterial aggregation and enhanced bacterial phagocytosis by macrophages (<i>p</i> &#x3c; 0.05)<i>.</i> Furthermore, human ME epithelial cells showed a dose-dependent increased expression of NLRP3 and SP-D proteins after LPS treatment. We conclude that SP-D plays a critical role in innate immunity and disease resolution through enhancing host defense and regulating inflammatory NF-κB and NLRP3 activation in experimental OM mice.

scholarly journals Innate immunity of surfactant protein A in experimental otitis media

2019 ◽  
Vol 25 (7) ◽  
pp. 391-400
Author(s):  
Osama Abdel-Razek ◽  
Lan Ni ◽  
Fengyong Yang ◽  
Guirong Wang
Keyword(s):  
Otitis Media ◽  
Protein A ◽  
Acute Otitis Media ◽  
Inflammatory Cells ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Control Group ◽  
Mucosal Thickness

Surfactant protein A (SP-A) plays an important role in innate immune response and host defense against various microorganisms through opsonization and complement activation. To investigate the role of SP-A in non-typeable Haemophilus influenzae (NTHi)-induced acute otitis media, this study used wild type C57BL/6 (WT) and SP-A knockout (KO) mice. We divided mice into an infection group in which the middle ear (ME) was injected with NTHi and a control group that received the same treatment using normal saline. Mice were sacrificed on d 1, 3, and 7 after treatment. Temporal bone samples were fixed for histological, cellular, and molecular analyses. Ear washing fluid (EWF) was collected for culture and analyses of pro-inflammatory cytokines and inflammatory cells. SP-A-mediated bacterial aggregation and killing and phagocytosis by macrophages were studied in vitro. SP-A expression was detected in the ME and Eustachian tube mucosa of WT mice but not KO mice. After infection, KO mice showed more severe inflammation evidenced by increased ME mucosal thickness and inflammatory cell infiltration and higher NF-κB activation compared to WT mice. The levels of IL-6 and IL-1β in the EWF of infected KO mice were higher compared to infected WT mice on d 1. Our studies demonstrated that SP-A mediated NTHi aggregation and killing and enhanced bacterial phagocytosis by macrophages in vitro and modulated inflammation of the ME in otitis media in vivo.

Critical role for cross-linking of trimeric lectin domains of surfactant protein D in antiviral activity against influenza A virus

2008 ◽  
Vol 412 (2) ◽  
pp. 323-329 ◽  
Author(s):  
Tesfaldet Tecle ◽  
Mitchell R. White ◽  
Grith Sorensen ◽  
Donald Gantz ◽  
Nilgun Kacak ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Critical Role ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Cross Linking ◽  
Viral Neutralization ◽  
Neutralizing Activity

Collectins are multimeric host defence lectins with trimeric CRDs (carbohydrate-recognition domains) and collagen and N-terminal domains that form higher-order structures composed of four or more trimers. Recombinant trimers composed of only the CRD and adjacent neck domain (termed NCRD) retain binding activity for some ligands and mediate some functional activities. The lung collectin SP-D (surfactant protein D) has strong neutralizing activity for IAVs (influenza A viruses) in vitro and in vivo, however, the NCRD derived from SP-D has weak viral-binding ability and lacks neutralizing activity. Using a panel of mAbs (monoclonal antibodies) directed against the NCRD in the present study we show that mAbs binding near the lectin site inhibit antiviral activity of full-length SP-D, but mAbs which bind other sites on the CRD do not. Two of the non-blocking mAbs significantly increased binding and antiviral activity of NCRDs as assessed by haemagglutination and neuraminidase inhibition and by viral neutralization. mAb-mediated cross-linking also enabled NCRDs to induce viral aggregation and to increase viral uptake by neutrophils and virus-induced respiratory burst responses by these cells. These results show that antiviral activities of SP-D can be reproduced without the N-terminal and collagen domains and that cross-linking of NCRDs is essential for antiviral activity of SP-D with respect to IAV.

scholarly journals Surfactant Protein D, a Marker of Lung Innate Immunity, Is Positively Associated With Insulin Sensitivity

Diabetes Care ◽  
2010 ◽  
Vol 33 (4) ◽  
pp. 847-853 ◽  
Author(s):  
J. M. Fernandez-Real ◽  
S. Valdes ◽  
M. Manco ◽  
B. Chico ◽  
P. Botas ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Insulin Sensitivity ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Lung Innate Immunity

scholarly journals ATF3 Protects against LPS-Induced Inflammation in Mice via Inhibiting HMGB1 Expression

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Pei-Fang Lai ◽  
Ching-Feng Cheng ◽  
Heng Lin ◽  
Tzu-Ling Tseng ◽  
Hsi-Hsien Chen ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Gene Knockout ◽  
Critical Role ◽  
Negative Regulator ◽  
Tlr4 Signaling ◽  
Lps Challenge ◽  
Hmgb1 Expression ◽  
Elevated Expression ◽  
Sepsis Therapy

Lipopolysaccharide (LPS) triggers innate immunity mainly via TLR4 signaling. ATF3 is a negative regulator of TLR4 signaling. HMGB1 plays a critical role in the final step of sepsis. However, the mechanisms of ATF3 and the role of HMGB1 in regulating innate immunity-induced sepsis are incompletely understood. In this study, we found that serum HMGB1 levels were 10-fold higher in patients with sepsis than normal controls. We further demonstrated that ATF3 gene knockout in mice subjected to LPS-induced endotoxemia correlates with an increase in the mortality rate and the elevated expression of IL-6, TNF-α, NO, MCP-1, and HMGB1 in the lung tissues or serum. The biochemical effects of ATF3 were observed inin vitromacrophages and blocked by ATF3 siRNA treatment. We have also shown that adeno-associated virus-mediated ATF3 gene transfer protected ATF3 knockout mice from LPS-induced mortality. In addition, ATF3 knockdown increased LPS-induced release of HMGB1. In conclusion, upregulation of ATF3 contributes to the reduced release of inflammatory molecules, especially HMGB1, which induced lung injury and increased the survival rate of mice after LPS challenge. Therefore, suppressing LPS-induced inflammation with ATF3 induction or ATF3 mimetics may be an important strategy for sepsis therapy.

Pulmonary dysfunction in neonatal SP-B-deficient mice

1997 ◽  
Vol 273 (4) ◽  
pp. L875-L882 ◽  
Author(s):  
Keisuke Tokieda ◽  
Jeffrey A. Whitsett ◽  
Jean C. Clark ◽  
Timothy E. Weaver ◽  
Kazushige Ikeda ◽  
...  
Keyword(s):  
Critical Role ◽  
Protein A ◽  
Surfactant Protein ◽  
Lung Compliance ◽  
Phospholipid Content ◽  
Surfactant Protein D ◽  
Intratracheal Administration ◽  
Lung Expansion ◽  
B Mice ◽  
Deficient Mice

Pulmonary function was assessed in newborn wild-type and homozygous and heterozygous surfactant protein B (SP-B)-deficient mice after birth. SP-B+/+ and SP-B+/− mice became well oxygenated and survived postnatally. Although lung compliance was decreased slightly in the SP-B+/− mice, lung volumes and compliances were decreased markedly in homozygous SP-B−/− mice. They died rapidly after birth, failing to inflate their lungs or oxygenate. SP-B proprotein was absent in the SP-B−/− mice and was reduced in the SP-B+/− mice, as assessed by Western analysis. Surfactant protein A, surfactant proprotein C, surfactant protein D, and surfactant phospholipid content in lungs from SP-B+/− and SP-B−/− mice were not altered. Lung saturated phosphatidylcholine and precursor incorporation into saturated phosphatidylcholine were not influenced by SP-B genotype. Intratracheal administration of perfluorocarbon resulted in lung expansion, oxygenation, and prolonged survival of SP-B−/− mice and in reduced lung compliance in SP-B+/+ and SP-B+/− mice. Lack of SP-B caused respiratory failure at birth, and decreased SP-B protein was associated with reduced lung compliance. These findings demonstrate the critical role of SP-B in perinatal adaptation to air breathing.

scholarly journals Critical role of amino acid position 343 of surfactant protein-D in the selective binding of glycolipids from Mycobacterium tuberculosis

Glycobiology ◽  
2009 ◽  
Vol 19 (12) ◽  
pp. 1473-1484 ◽  
Author(s):  
Tracy K Carlson ◽  
Jordi B Torrelles ◽  
Kelly Smith ◽  
Tim Horlacher ◽  
Riccardo Castelli ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Amino Acid ◽  
Critical Role ◽  
Amino Acid Position ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Selective Binding

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.

Sign in / Sign up

Export Citation Format

Share Document