scholarly journals Adherence of Streptococcus pneumoniae to Respiratory Epithelial Cells Is Inhibited by Sialylated Oligosaccharides

1998 ◽  
Vol 66 (4) ◽  
pp. 1439-1444 ◽  
Author(s):  
Roger Barthelson ◽  
Ali Mobasseri ◽  
David Zopf ◽  
Paul Simon
Keyword(s):  
Streptococcus Pneumoniae ◽  
Human Serum Albumin ◽  
Epithelial Cells ◽  
Serum Albumin ◽  
Human Serum ◽  
Cell Line ◽  
Airway Epithelial Cells ◽  
Logarithmic Phase ◽  
Respiratory Epithelial Cells ◽  
Respiratory Epithelial

ABSTRACT To study carbohydrate-mediated adherence of Streptococcus pneumoniae to the human airway, we measured binding of liveS. pneumoniae organisms to a cultured cell line derived from the lining of the conjunctiva and to primary monolayers of human bronchial epithelial cells in the presence and absence of oligosaccharide inhibitors. Both encapsulated and nonencapsulated strains of S. pneumoniae grown to mid-logarithmic phase in suspension culture adhered to cultured primary respiratory epithelial cells and the conjunctival cell line. Adherence of nine clinically prevalent S. pneumoniaecapsular types studied was inhibited preferentially by sialylated oligosaccharides that terminate with the disaccharide NeuAcα2-3(or 6)Galβ1. Adherence of some strains also was weakly inhibited by oligosaccharides that terminate with lactosamine (Galβ1-4GlcNAcβ1). When sialylated oligosaccharides were covalently coupled to human serum albumin at a density of approximately 20 oligosaccharides per molecule of protein, the molar inhibitory potency of the oligosaccharide inhibitor was enhanced 500-fold. The above-mentioned experiments reveal a previously unreported dependence upon sialylated carbohydrate ligands for adherence of S. pneumoniae to human upper airway epithelial cells. Enhanced inhibitory potencies of polyvalent over monovalent forms of oligosaccharide inhibitors of adherence suggest that the putative adhesin(s) that recognizes the structure NeuAcα2-3(or 6)Galβ1 is arranged on the bacterial surface in such a manner that it may be cross-linked by oligosaccharides covalently linked to human serum albumin.

scholarly journals Interaction of Arylidenechromanone/Flavanone Derivatives with Biological Macromolecules Studied as Human Serum Albumin Binding, Cytotoxic Effect, Biocompatibility Towards Red Blood Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3172 ◽  
Author(s):  
Angelika A. Adamus-Grabicka ◽  
Magdalena Markowicz-Piasecka ◽  
Michał B. Ponczek ◽  
Joachim Kusz ◽  
Magdalena Małecka ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Red Blood Cells ◽  
Human Serum ◽  
Cell Line ◽  
Cell Lines ◽  
Blood Cells ◽  
Cytotoxic Effect ◽  
Human Leukemia ◽  
Ic50 Values

The aim of this study was to determine the cytotoxic effect of 3-arylidenechromanone (1) and 3arylideneflavanone (2) on HL-60 and NALM-6 cell lines (two human leukemia cell lines) and a WM-115 melanoma cell line. Both compounds exhibited high cytotoxic activity with higher cytotoxicity exerted by compound 2, for which IC50 values below 10 µM were found for each cell line. For compound 1, the IC50 values were higher than 10 µM for HL-60 and WM-115 cell lines, but IC50 < 10 µM was found for the NALM-6 cell line. Both compounds, at the concentrations close to IC50 (concentration range: 5–24 µM/L for compound 1 and 6–10 µM/L for compound 2), are not toxic towards red blood cells. The synthesized compounds were characterized using spectroscopic methods 1H- and 13C-NMR, IR, MS, elemental analysis, and X-ray diffraction. The lipophilicity of both synthesized compounds was determined using an RP-TLC method and the logP values found were compared with the theoretical ones taken from the Molinspiration Cheminformatics (miLogP) software package. The mode of binding of both compounds to human serum albumin was assessed using molecular docking methods.

Pyrazolo[3,4-d]pyrimidines-loaded human serum albumin (HSA) nanoparticles: Preparation, characterization and cytotoxicity evaluation against neuroblastoma cell line

2017 ◽  
Vol 27 (14) ◽  
pp. 3196-3200 ◽  
Author(s):  
Anna Lucia Fallacara ◽  
Arianna Mancini ◽  
Claudio Zamperini ◽  
Elena Dreassi ◽  
Stefano Marianelli ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Cell Line ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line

Respiratory epithelial cells regulate lung inflammation in response to inhaled endotoxin

2004 ◽  
Vol 287 (1) ◽  
pp. L143-L152 ◽  
Author(s):  
Shawn J. Skerrett ◽  
H. Denny Liggitt ◽  
Adeline M. Hajjar ◽  
Robert K. Ernst ◽  
Samuel I. Miller ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Response ◽  
Transgenic Mice ◽  
Lung Inflammation ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Respiratory Epithelial Cells ◽  
Distal Airway ◽  
Tnf Α ◽  
Respiratory Epithelial

To determine the role of respiratory epithelial cells in the inflammatory response to inhaled endotoxin, we selectively inhibited NF-κB activation in the respiratory epithelium using a mutant IκB-α construct that functioned as a dominant negative inhibitor of NF-κB translocation (dnIκB-α). We developed two lines of transgenic mice in which expression of dnIκB-α was targeted to the distal airway epithelium using the human surfactant apoprotein C promoter. Transgene expression was localized to the epithelium of the terminal bronchioles and alveoli. After inhalation of LPS, nuclear translocation of NF-κB was evident in bronchiolar epithelium of nontransgenic but not of transgenic mice. This defect was associated with impaired neutrophilic lung inflammation 4 h after LPS challenge and diminished levels of TNF-α, IL-1β, macrophage inflammatory protein-2, and KC in lung homogenates. Expression of TNF-α within bronchiolar epithelial cells and of VCAM-1 within peribronchiolar endothelial cells was reduced in transgenic animals. Thus targeted inhibition of NF-κB activation in distal airway epithelial cells impaired the inflammatory response to inhaled LPS. These data provide causal evidence that distal airway epithelial cells and the signals they transduce play a physiological role in lung inflammation in vivo.

Cell-specific involvement of HNF-1β in α1-antitrypsin gene expression in human respiratory epithelial cells

2002 ◽  
Vol 282 (4) ◽  
pp. L757-L765 ◽  
Author(s):  
Chaobin Hu ◽  
David H. Perlmutter
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Cell Line ◽  
Primary Cultures ◽  
Synergistic Action ◽  
Intestinal Epithelial ◽  
Hep G2 ◽  
Respiratory Epithelial Cells ◽  
Human Respiratory Epithelial Cells ◽  
Respiratory Epithelial

The synergistic action of hepatocyte nuclear factor (HNF)-1α and HNF-4 plays an important role in expression of the α1-antitrypsin (α1-AT) gene in human hepatic and intestinal epithelial cells. Recent studies have indicated that the α1-AT gene is also expressed in human pulmonary alveolar epithelial cells, a potentially important local site of the lung antiprotease defense. In this study, we examined the possibility that α1-AT gene expression in a human pulmonary epithelial cell line H441 was also directed by the synergistic action of HNF-1α and HNF-4 and/or by the action of HNF-3, which has been shown to play a dominant role in gene expression in H441 cells. The results show that α1-AT gene expression in H441 cells is predominantly driven by HNF-1β, even though HNF-1β has no effect on α1-AT gene expression in human hepatic Hep G2 and human intestinal epithelial Caco-2 cell lines. Expression of α1-AT and HNF-1β was also demonstrated in primary cultures of human respiratory epithelial cells. HNF-4 has no effect on α1-AT gene expression in H441 cells, even when it is cotransfected with HNF-1β or HNF-1α. HNF-3 by itself has little effect on α1-AT gene expression in H441, Hep G2, or Caco-2 cells but tends to have an upregulating effect when cotransfected with HNF-1 in Hep G2 and Caco-2 cells. These results indicate the unique involvement of HNF-1β in α1-AT gene expression in a cell line and primary cultures derived from human respiratory epithelium.

scholarly journals Differential Role of CbpA and PspA in Modulation of In Vitro CXC Chemokine Responses of Respiratory Epithelial Cells to Infection with Streptococcus pneumoniae

2006 ◽  
Vol 74 (12) ◽  
pp. 6739-6749 ◽  
Author(s):  
Rikki M. A. Graham ◽  
James C. Paton
Keyword(s):  
Streptococcus Pneumoniae ◽  
Epithelial Cells ◽  
Deletion Mutant ◽  
Protein A ◽  
A549 Cells ◽  
Respiratory Pathogens ◽  
Respiratory Epithelial Cells ◽  
Cxc Chemokine ◽  
Respiratory Epithelial

ABSTRACTRespiratory epithelial cells play an active part in the host response to respiratory pathogens, such asStreptococcus pneumoniae, by releasing chemokines responsible for neutrophil recruitment. In order to investigate the role of specific pneumococcal virulence factors in eliciting CXC chemokine responses, type II pneumocytes (A549) and nasopharyngeal cells (Detroit-562) were infected withS. pneumoniaeD39 or mutants lacking choline-binding protein A (CbpA), pneumococcal surface protein A (PspA), or specific domains thereof. In response to wild-type D39, both A549 and Detroit-562 cells showed a significant increase in CXC chemokine mRNA and interleukin-8 protein. This response was increased twofold when acbpAdeletion mutant (ΔCbpA) was used, suggesting that CbpA inhibits CXC chemokine induction. All three N-terminal domains of CbpA are required for this effect, as in-frame deletion of the respective region ofcbpAhad the same effect on the CXC chemokine response as deletion ofcbpAaltogether. Infection with apspAdeletion mutant (ΔPspA) led to a twofold decrease in the CXC chemokine response of A549 but not Detroit-562 cells, compared to infection with D39 at 2 h. Thus, PspA appears to have the ability to stimulate early CXC chemokine release from A549 cells. Deletion of the region ofpspAencoding the first N-terminal α-helical domain reduced the ability ofS. pneumoniaeto elicit a chemokine response to the same degree as deletion ofpspAaltogether. Thus, the N termini of CbpA and PspA exert differential effects on CXC chemokine induction in epithelial cells infected withS. pneumoniae.

scholarly journals Moxifloxacin and Azithromycin but not Amoxicillin Protect Human Respiratory Epithelial Cells against Streptococcus pneumoniae In Vitro when Administered up to 6 Hours after Challenge

2005 ◽  
Vol 49 (12) ◽  
pp. 5119-5122 ◽  
Author(s):  
Martina Ulrich ◽  
Cordula Albers ◽  
Jan-Georg Möller ◽  
Axel Dalhoff ◽  
Gisela Korfmann ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Epithelial Cells ◽  
Protective Effect ◽  
Respiratory Epithelial Cells ◽  
Human Respiratory Epithelial Cells ◽  
Respiratory Cells ◽  
Respiratory Epithelial

ABSTRACT We determined the protective effect of moxifloxacin, azithromycin, and amoxicillin against Streptococcus pneumoniae infection of respiratory cells. Moxifloxacin and azithromycin effectively killed intracellular S. pneumoniae strains and protected respiratory epithelial cells significantly even when given 6 h after S. pneumoniae challenge. Amoxicillin was less effective.

scholarly journals Hydrogen Sulfide Inhibits TMPRSS2 in Human Airway Epithelial Cells: Implications for SARS-CoV-2 Infection

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1273
Author(s):  
Giulia Pozzi ◽  
Elena Masselli ◽  
Giuliana Gobbi ◽  
Prisco Mirandola ◽  
Luis Taborda-Barata ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Surface Proteins ◽  
Lower Airway ◽  
Target Cells ◽  
Airway Epithelial ◽  
Respiratory Epithelial Cells ◽  
Respiratory Epithelial

The COVID-19 pandemic has now affected around 190 million people worldwide, accounting for more than 4 million confirmed deaths. Besides ongoing global vaccination, finding protective and therapeutic strategies is an urgent clinical need. SARS-CoV-2 mostly infects the host organism via the respiratory system, requiring angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) to enter target cells. Therefore, these surface proteins are considered potential druggable targets. Hydrogen sulfide (H2S) is a gasotransmitter produced by several cell types and is also part of natural compounds, such as sulfurous waters that are often inhaled as low-intensity therapy and prevention in different respiratory conditions. H2S is a potent biological mediator, with anti-oxidant, anti-inflammatory, and, as more recently shown, also anti-viral activities. Considering that respiratory epithelial cells can be directly exposed to H2S by inhalation, here we tested the in vitro effects of H2S-donors on TMPRSS2 and ACE2 expression in human upper and lower airway epithelial cells. We showed that H2S significantly reduces the expression of TMPRSS2 without modifying ACE2 expression both in respiratory cell lines and primary human upper and lower airway epithelial cells. Results suggest that inhalational exposure of respiratory epithelial cells to natural H2S sources may hinder SARS-CoV-2 entry into airway epithelial cells and, consequently, potentially prevent the virus from spreading into the lower respiratory tract and the lung.

Sign in / Sign up

Export Citation Format

Share Document