scholarly journals Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels

10.3791/55800 ◽  
2017 ◽  
Author(s):  
Helene M. Wolsk ◽  
Bo L. Chawes ◽  
Jonathan Thorsen ◽  
Jakob Stokholm ◽  
Klaus Bønnelykke ◽  
...  
Keyword(s):  
Upper Airway ◽  
Noninvasive Sampling ◽  
Immune Mediator ◽  
Mucosal Lining

Cyclic Adenosine Monophosphate Stimulation of Mucociliary Activity in the Upper Airways in Vivo

1995 ◽  
Vol 104 (5) ◽  
pp. 388-393 ◽  
Author(s):  
Anders Cervin ◽  
Sven Lindberg ◽  
Jan Dolata ◽  
Ulf Mercke
Keyword(s):  
Upper Airway ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Airway Disease ◽  
Maxillary Artery ◽  
Dibutyryl Camp ◽  
Upper Airways ◽  
Maximum Increase ◽  
Xanthine Derivatives

Xanthine derivatives are known to accelerate mucociliary transport in the lower airways, probably by preventing degradation of cyclic adenosine monophosphate (cAMP) and thereby increasing its intracellular concentration. The purpose of this study was to investigate the effects of cAMP on mucociliary activity in the upper airways. The effect on the mucociliary activity in the rabbit maxillary sinus of the xanthine derivatives theophylline and enprophylline was compared to that of the cAMP analog dibutyryl cAMP. The compounds were administered into the maxillary artery, and the response was recorded with a photoelectric technique. Infusions of theophylline (1.0 and 10 mg/kg) increased mucociliary activity (22.8% ± 5.9%, n = 6, and 21.6% ± 4.9%, n = 7, p < .05, respectively). Infusions of enprophylline (1.0 and 10.0 mg/kg) accelerated mucociliary activity (at the highest dosage tested, 24.3% ± 4.1%). Infusions of dibutyryl cAMP (0.1 and 1.0 mg/kg) stimulated mucociliary activity, with the maximum increase (20.1% ± 3.0%, n = 13, p < .05) being observed at a dosage of 0.1 mg/kg. The infused substances increased mucociliary activity within 1 minute after the start of the infusion, the duration of the response being approximately 20 minutes for theophylline, 22 minutes for enprophylline, and 12 minutes for dibutyryl cAMP. The present results support the view that cAMP is involved in regulating mucociliary activity in the upper airways. It remains to be elucidated whether xanthines such as theophylline and enprophylline are beneficial in upper airway disease in which mucociliary function is impaired (eg, chronic sinusitis).

scholarly journals Cdc42 Promotes Host Defenses against Fatal Infection

2013 ◽  
Vol 81 (8) ◽  
pp. 2714-2723 ◽  
Author(s):  
Keunwook Lee ◽  
Kelli L. Boyd ◽  
Diptiben V. Parekh ◽  
Thomas E. Kehl-Fie ◽  
H. Scott Baldwin ◽  
...  
Keyword(s):  
Rho Gtpase ◽  
Critical Role ◽  
Upper Airway ◽  
Specific Protein ◽  
Small Gtpase ◽  
Host Protection ◽  
Cell Functions ◽  
Airway Infections ◽  
Multiple Cell

ABSTRACTThe small Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, invasion, migration, differentiation, and morphogenesis. As the role of Cdc42-dependent signaling in fibroblastsin vivois unknown, we attempted to specifically delete it in these cells by crossing the Cdc42fl/flmouse with an fibroblast-specific protein 1 (FSP1)-Cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP1-Cre;Cdc42fl/flmice died at 3 weeks of age due to overwhelming suppurative upper airway infections that were associated with neutrophilia and lymphopenia. Even though major aberrations in lymphoid tissue development were present in the mice, the principal cause of death was severe migration and killing abnormalities of the neutrophil population resulting in an inability to control infection. We also show that in addition to fibroblasts, FSP1-Cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this nonspecific Cre mouse, we inadvertently demonstrated the importance of Cdc42 in host protection from lethal infections and suggest a critical role for this small GTPase in innate immunity.

scholarly journals Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

2021 ◽  
Author(s):  
Luz Garcia-Alonso ◽  
Louis-François Handfield ◽  
Kenny Roberts ◽  
Konstantina Nikolakopoulou ◽  
Ridma C. Fernando ◽  
...  
Keyword(s):  
Cell Fate ◽  
Spatial Dynamics ◽  
Dynamic Changes ◽  
Spatial Reference ◽  
Mucosal Lining ◽  
Temporal And Spatial ◽  
Notch Pathways ◽  
Differentiation Efficiency

AbstractThe endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated single-cell and spatial reference maps of the human uterus and 3D endometrial organoid cultures. We dissect the signalling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids highlights common pathways regulating the differentiation of secretory and ciliated lineage in vivo and in vitro. We show in vitro that downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. These mechanistic insights provide a platform for future development of treatments for a range of common endometrial disorders including endometriosis and carcinoma.

scholarly journals IRAK2, an IL1R/TLR Immune Mediator, Enhances Radiosensitivity via Modulating Caspase 8/3-Mediated Apoptosis in Oral Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Chih-Chia Yu ◽  
Michael W.Y. Chan ◽  
Hon-Yi Lin ◽  
Wen-Yen Chiou ◽  
Ru-Inn Lin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Local Control ◽  
Squamous Cell ◽  
Expression Profiles ◽  
Caspase 8 ◽  
Immune Mediator

Predicting and overcoming radioresistance are crucial in radiation oncology, including in managing oral squamous cell carcinoma (OSCC). First, we used RNA-sequence to compare expression profiles of parent OML1 and radioresistant OML1-R OSCC cells in order to select candidate genes responsible for radiation sensitivity. We identified IRAK2, a key immune mediator of the IL-1R/TLR signaling, as a potential target in investigating radiosensitivity. In four OSCC cell lines, we observed that intrinsically low IRAK2 expression demonstrated a radioresistant phenotype (i.e., OML1-R and SCC4), and vice versa (i.e., OML1 and SCC25). Next, we overexpressed IRAK2 in low IRAK2-expression OSCC cells and knocked it down in high IRAK2-expression cells to examine changes of irradiation response. After ionizing radiation (IR) exposure, IRAK2 overexpression enhanced the radiosensitivity of radioresistant cells and synergistically suppressed OSCC cell growth both in vitro and in vivo, and vice versa. We found that IRAK2 overexpression restored and enhanced radiosensitivity by enhancing IR-induced cell killing via caspase-8/3-dependent apoptosis. OSCC patients with high IRAK2 expression had better post-irradiation local control than those with low expression (i.e., 87.4% vs. 60.0% at five years, P = 0.055), showing that IRAK2 expression was associated with post-radiation recurrence. Multivariate analysis confirmed high IRAK2 expression as an independent predictor for local control (HR, 0.11; 95% CI, 0.016 – 0.760; P = 0.025). In conclusion, IRAK2 enhances radiosensitivity, via modulating caspase 8/3-medicated apoptosis, potentially playing double roles as a predictive biomarker and a novel therapeutic target in OSCC.

scholarly journals In-vitro virucidal activity of hypothiocyanite and hypothiocyanite/lactoferrin mix against SARS-CoV-2

2020 ◽  
Author(s):  
Luca Cegolon ◽  
Mattia Mirandola ◽  
Claudio Salaris ◽  
Maria Vittoria Salvati ◽  
Cristiano Salata ◽  
...  
Keyword(s):  
Upper Airway ◽  
In Vitro Study ◽  
Alveolar Type ◽  
Virucidal Activity ◽  
Human Immune System ◽  
Pharmacological Interventions ◽  
Protection Measures ◽  
Viral Spread

ABSTRACTSARS-CoV-2 replicates efficiently in the upper airway during prodromal stage with resulting viral shedding into the environment from patients with active disease as well as from asymptomatic individuals. So far, virus spread has been exclusively contained by non-pharmacological interventions (social distancing, face masks, hand washing and several measures limiting business activities or movement of individuals)1,2. There is a need to find pharmacological interventions to mitigate the viral spread, supporting yet limiting the existing health protection measures while an effective and safe vaccine will hopefully become available. Hypothiocyanite and lactoferrin as part of the innate human immune system were shown to have a large spectrum of cidal activity against bacteria, fungi and viruses2,3. To test their virucidal activity against SARS-CoV-2 we conducted an in-vitro study. Here we show a dose-dependent virucidal activity of hypothiocyanite at micromolar concentrations, slightly improved by the presence of lactoferrin. The two substances are devoid of any cytotoxicity and may be administered combined by aerosol to exploit their antiviral activity at the port of entry (mouth, nasal cavity, conjunctiva) or exit (mouth, through emission of respiratory droplets) of SARS-CoV-2 in the human body. Furthermore, aerosol with hypothiocyanite and lactoferrin combined could also have a therapeutic effect in the lower respiratory tract, at the level of gas exchange units of the lung, preventing the devastating infection of alveolar type II cells where ACE2 is highly expressed. An in-vivo validation of in-vitro results is urgently required.

scholarly journals REGN-COV2 antibody cocktail prevents and treats SARS-CoV-2 infection in rhesus macaques and hamsters

2020 ◽  
Author(s):  
Alina Baum ◽  
Richard Copin ◽  
Dharani Ajithdoss ◽  
Anbo Zhou ◽  
Kathryn Lanza ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Therapeutic Potential ◽  
Rhesus Macaques ◽  
Upper Airway ◽  
Spike Protein ◽  
In Vivo Efficacy ◽  
Virus Load ◽  
Golden Hamsters ◽  
Antibody Cocktail

AbstractAn urgent global quest for effective therapies to prevent and treat COVID-19 disease is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987+REGN10933) targeting non-overlapping epitopes on the SARS-CoV-2 spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques and golden hamsters and demonstrate that REGN-COV-2 can greatly reduce virus load in lower and upper airway and decrease virus induced pathological sequalae when administered prophylactically or therapeutically. Our results provide evidence of the therapeutic potential of this antibody cocktail.

Preliminary results on in-vivo imaging of upper airway inhalation injuries using anatomical optical coherence tomography

2017 ◽  
Author(s):  
Anthony Phan ◽  
Karol Karnowski ◽  
Qingyun Lee ◽  
Peter Fejes ◽  
Bryden Quirk ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
In Vivo Imaging ◽  
Upper Airway ◽  
Optical Coherence ◽  
Preliminary Results

Effect of surface tension of mucosal lining liquid on upper airway mechanics in anesthetized humans

2003 ◽  
Vol 95 (1) ◽  
pp. 357-363 ◽  
Author(s):  
Jason P. Kirkness ◽  
Peter R. Eastwood ◽  
Irene Szollosi ◽  
Peter R. Platt ◽  
John R. Wheatley ◽  
...  
Keyword(s):  
Surface Tension ◽  
Human Subjects ◽  
Upper Airway ◽  
Exogenous Surfactant ◽  
Airway Mechanics ◽  
Before And After ◽  
Airway Opening ◽  
Mucosal Lining ◽  
Effect Of Surface

Upper airway (UA) patency may be influenced by surface tension (γ) operating within the (UAL). We examined the role of γ of UAL in the maintenance of UA patency in eight isoflurane-anesthetized supine human subjects breathing via a nasal mask connected to a pneumotachograph attached to a pressure delivery system. We evaluated 1) mask pressure at which the UA closed (Pcrit), 2) UA resistance upstream from the site of UA collapse (RUS), and 3) mask pressure at which the UA reopened (Po). A multiple pressure-transducer catheter was used to identify the site of airway closure (velopharyngeal in all subjects). UAL samples (0.2 μl) were collected, and the γ of UAL was determined by using the “pull-off force” technique. Studies were performed before and after the intrapharyngeal instillation of 5 ml of exogenous surfactant (Exosurf, Glaxo Smith Kline). The γ of UAL decreased from 61.9 ± 4.1 (control) to 50.3 ± 5.0 mN/m (surfactant; P < 0.02). Changes in Po, RUS, and Po - Pcrit (change = control - surfactant) were positively correlated with changes in γ ( r2 > 0.6; P < 0.02) but not with changes in Pcrit ( r2 = 0.4; P > 0.9). In addition, mean peak inspiratory airflow (no flow limitation) significantly increased ( P < 0.04) from 0.31 ± 0.06 (control) to 0.36 ± 0.06 l/s (surfactant). These findings suggest that γ of UAL exerts a force on the UA wall that hinders airway opening. Instillation of exogenous surfactant into the UA lowers the γ of UAL, thus increasing UA patency and augmenting reopening of the collapsed airway.

scholarly journals Reassortment between Avian H5N1 and Human H3N2 Influenza Viruses in Ferrets: a Public Health Risk Assessment

2009 ◽  
Vol 83 (16) ◽  
pp. 8131-8140 ◽  
Author(s):  
Sara Jackson ◽  
Neal Van Hoeven ◽  
Li-Mei Chen ◽  
Taronna R. Maines ◽  
Nancy J. Cox ◽  
...  
Keyword(s):  
Upper Airway ◽  
Influenza Viruses ◽  
Upper Respiratory Tract ◽  
Upper Airways ◽  
Nasal Secretions ◽  
H5 Subtype ◽  
H3n2 Influenza ◽  
Human Viruses ◽  
Reassortant Viruses

ABSTRACT This study investigated whether transmissible H5 subtype human-avian reassortant viruses could be generated in vivo. To this end, ferrets were coinfected with recent avian H5N1 (A/Thailand/16/04) and human H3N2 (A/Wyoming/3/03) viruses. Genotype analyses of plaque-purified viruses from nasal secretions of coinfected ferrets revealed that approximately 9% of recovered viruses contained genes from both progenitor viruses. H5 and H3 subtype viruses, including reassortants, were found in airways extending toward and in the upper respiratory tract of ferrets. However, only parental H5N1 genotype viruses were found in lung tissue. Approximately 34% of the recovered reassortant viruses possessed the H5 hemagglutinin (HA) gene, with five unique H5 subtypes recovered. These H5 reassortants were selected for further studies to examine their growth and transmissibility characteristics. Five H5 viruses with representative reassortant genotypes showed reduced titers in nasal secretions of infected ferrets compared to the parental H5N1 virus. No transmission by direct contact between infected and naïve ferrets was observed. These studies indicate that reassortment between H5N1 avian influenza and H3N2 human viruses occurred readily in vivo and furthermore that reassortment between these two viral subtypes is likely to occur in ferret upper airways. Given the relatively high incidence of reassortant viruses from tissues of the ferret upper airway, it is reasonable to conclude that continued exposure of humans and animals to H5N1 alongside seasonal influenza viruses increases the risk of generating H5 subtype reassortant viruses that may be shed from upper airway secretions.

scholarly journals Serotonergic Modulation of Inspiratory Hypoglossal Motoneurons in Decerebrate Dogs

2006 ◽  
Vol 95 (6) ◽  
pp. 3449-3459 ◽  
Author(s):  
Ivo F. Brandes ◽  
Edward J. Zuperku ◽  
Astrid G. Stucke ◽  
Danica Jakovcevic ◽  
Francis A. Hopp ◽  
...  
Keyword(s):  
Upper Airway ◽  
Discharge Pattern ◽  
Receptor Subtype ◽  
Drug Induced ◽  
Airway Patency ◽  
Hypoglossal Motoneurons ◽  
Single Neuron Recording ◽  
Induced Changes

Inspiratory hypoglossal motoneurons (IHMNs) maintain upper airway patency. However, this may be compromised during sleep and by sedatives, potent analgesics, and volatile anesthetics by either depression of excitatory or enhancement of inhibitory inputs. In vitro data suggest that serotonin (5-HT), through the 5-HT2A receptor subtype, plays a key role in controlling the excitability of IHMNs. We hypothesized that in vivo 5-HT modulates IHMNs activity through the 5-HT2A receptor subtype. To test this hypothesis, we used multibarrel micropipettes for extracellular single neuron recording and pressure picoejection of 5-HT or ketanserin, a selective 5-HT2A receptor subtype antagonist, onto single IHMNs in decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs. Drug-induced changes in neuronal discharge frequency ( Fn) and neuronal discharge pattern were analyzed using cycle-triggered histograms. 5-HT increased the control peak Fn to 256% and the time-averaged Fn to 340%. 5-HT increased the gain of the discharge pattern by 61% and the offset by 34 Hz. Ketanserin reduced the control peak Fn by 68%, the time-averaged Fn by 80%, and the gain by 63%. These results confirm our hypothesis that in vivo 5-HT is a potent modulator of IHMN activity through the 5-HT2A receptor subtype. Application of exogenous 5-HT shows that this mechanism is not saturated during hypercapnic hyperoxia. The two different mechanisms, gain modulation and offset change, indicate that 5-HT affects the excitability as well as the excitation of IHMNs in vivo.

Sign in / Sign up

Export Citation Format

Share Document