Inhaled Particulate Matter Affects Immune Responsiveness of Human Lung Phagocytes to Mycobacteria

2021 ◽  
Author(s):  
Brandon Anton Paarwater ◽  
Jomien Mouton ◽  
Samantha L Sampson ◽  
Stephanus T Malherbe ◽  
Jane A Shaw ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Post Infection ◽  
Ex Vivo ◽  
Early Time ◽  
Immune Responsiveness ◽  
Phenotypic Profile ◽  
Host Protection ◽  
Tnf Α ◽  
Long Term Impact

The influence of smoke- or air pollution-derived cytoplasmic particulate matter (PM) can be detrimental and lead to failed lung immunity. We investigated mycobacterial uptake, intracellular replication, and soluble immune mediator responses of human bronchoalveolar lavage cells (BALC) loaded with/without PM, to infection with mycobacterial strains. We observed that only BALC containing PM display an ex vivo phenotypic profile dominated by spontaneous interleukin (IL) -10 production. PM loaded BALC retained the ability to phagocytose both Mycobacterium bovis Bacille Calmette Guérin (BCG) and Mycobacterium tuberculosis (M.tb) ΔleuDΔpanCD at equal efficacy as clear non-PM loaded BALC. However, immune responsiveness, such as the production of IL-6 (p=0.015) and tumor necrosis factor (TNF)-α (p= 0.0172) immediately post M.bovis BCG infection, were dramatically lower in black BALC loaded with PM versus clear non-PM loaded BALC. By 24 hour post infection, differential immune responses to M.bovis BCG between black versus clear BALC waned, and instead, production of IL-6 (p= 0.03) and IL-1α (p= 0.04 ) by black BALC were lower versus clear BALC following M.tb ΔleuDΔpanCD infection. Considering that TNFα and IL-6 are characterized as critical to host protection against mycobacteria, our findings suggest that BALC loaded with inhaled PM, display lower levels of anti-mycobacterial mediators, and that the response magnitude differs according to infective mycobacterial strain. Even though this did not translate into altered mycobacterial killing at early time points post infection, the long-term impact of such changes remains to be established.

Generation of TNFα and Interleukin-6 by Peritoneal Macrophages after Overnight Dwells with Bicarbonate- or Lactate-Buffered Dialysis Fluid

2002 ◽  
Vol 22 (6) ◽  
pp. 663-669 ◽  
Author(s):  
Tomasz Liberek ◽  
Monika Lichodziejewska–Niemierko ◽  
Wanda Knopinska–Posluszny ◽  
Thomas P. Schaub ◽  
Judith Kirchgessner ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Peritoneal Macrophages ◽  
Cytokine Release ◽  
Dialysis Fluid ◽  
Tnf Α ◽  
Peritoneal Dialysis Fluid ◽  
Initial Ph ◽  
Elisa Technique

Objective In order to evaluate the biocompatibility profile of a newly designed peritoneal dialysis fluid (PDF), we evaluated peritoneal leukocyte (PMΦ) cytokine release following overnight in vivo dwells using standard, lactate-buffered, single-chamber bag PDF (Lac-PDF) and purely bicarbonate-buffered, double-chamber bag PDF containing 34 (Bic-PDF) or 39 (Bic Hi-PDF) mmol/L bicarbonate. Design A randomized, open, crossover clinical trial with single weekly test dwells was performed in stable, long-term continuous ambulatory PD patients ( n = 8). During 8-hour overnight dwells, PMΦ were exposed to different PDF containing 1.5% glucose. After drainage, peritoneal cells were isolated and incubated with RPMI 1640 medium for 2 or 3 hours, with and without stimulation by lipopolysaccharide (LPS). Ex vivo release of tumor necrosis factor (TNF)-α and interleukin (IL)-6 was measured by specific ELISA technique. Results After pre-exposure to Lac-PDF, PMΦ generated 242 ± 279 pg TNFα/106 cells and 157 ± 105 pg IL-6/106 cells. When pre-exposed to Bic-PDF and Bic Hi-PDF, TNFα and IL-6 production of PMΦ was not significantly different from Lac-PDF. After LPS stimulation (100 ng/mL), PMΦ secretion of TNFα and IL-6 pre-exposed to three PDF revealed no significant differences between groups: TNFα was 2864 ± 1216, 2910 ± 1202, and 3291 ± 558 pg/106 cells after overnight dwells with Lac-PDF, Bic-PDF, and Bic Hi-PDF, respectively. Comparably, LPS-stimulated (100 pg/mL) PMΦ showed IL-6 secretion of 891 ± 335, 1380 ± 1149, and 1442 ± 966 pg/106 cells for Lac-PDF, Bic-PDF, and Bic Hi-PDF. Conclusion After long-term overnight dwells, initial pH, the different buffers, and varying glucose degradation product levels of PDF do not strongly affect PMΦ function with respect to cytokine release. The lack of significant differences between fluids may result from the complete dialysate equilibration achieved during the overnight intraperitoneal dwell.

scholarly journals Continuous Dialysis with Bicarbonate/Lactate-Buffered Peritoneal Dialysis Fluids Results in a Long-Term Improvement in Ex Vivo Peritoneal Macrophage Function

2002 ◽  
Vol 13 (suppl 1) ◽  
pp. S97-S103
Author(s):  
Suzanne Jones ◽  
Clifford J. Holmes ◽  
Ruth K. Mackenzie ◽  
Rachel Stead ◽  
Gerald A. Coles ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Macrophage ◽  
Ex Vivo ◽  
Negative Consequences ◽  
Necrosis Factor Alpha ◽  
Membrane Function ◽  
Neutral Ph ◽  
Tnf Α ◽  
Dialysis Fluids

ABSTRACT. To circumvent the potentially negative consequences of long-term exposure to unphysiologic acidic lactate-buffered peritoneal dialysis fluids (PDF), neutral pH solutions buffered with bicarbonate/lactate have recently been introduced in phase 2 and 3 clinical trials. This study examines the longitudinal changes in peritoneal macrophage (PMØ) function in patients dialyzed continuously with either lactate (LPD; 40 mM lactate, pH 5.2)-buffered or bicarbonate/lactate (TBL; 25 mM/15 mM bicarbonate/lactate, pH 7.3)-buffered PDF. Before the study, during the run in period of a phase 3 clinical trial, all patients had been taking LPD for at least the previous 18 wk. At the beginning of the study (day 0), both constitutive and serum-treated zymosan (STZ) stimulated tumor necrosis factor alpha (TNF-α) synthesis were assessed in PMØ isolated from 12-h dwell effluent (with 1.36% glucose) in all patients. The patients were subsequently randomized to either continuous TBL or LPD therapy and PMØ function was assessed after further 3- and 6-mo periods in all patients. At all time points measured STZ induced a dose-dependent increase in PMØ TNF-α secretion (P = 0.043 versus control for doses greater than 100 μg/ml). In patients continuously dialyzed with LPD, constitutive PMØ TNF-α synthesis levels (mean ± SEM, pg/106 PMØ per18 h, n = 5 patients) were 154 ± 65, 261 ± 60, and 101 ± 99 at 0, 3, and 6 mo, respectively. Stimulated STZ (1000 μg/ml) levels were 1340 ± 519, 1046 ± 586, and 758 ± 250 at 0, 3, and 6 mo, respectively. In patients dialyzed with TBL, constitutive PMØ TNF-α synthesis levels (pg/106 PMØ per 18 h, n = 5 patients) were 300 ± 136, 106 ± 35, and 213 ± 62 at 0, 3, and 6 mo, respectively. Stimulated STZ (1000 μg/ml) levels were 1969 ± 751, 1541 ± 330, and 2670 ± 671 at 0, 3, and 6 mo, respectively. At 6 mo, STZ-stimulated PMØ TNF-α synthesis was significantly higher in patients treated with TBL compared with those treated with LPD (P = 0.0035). These data suggest that in patients continuously dialyzed with a neutral pH solution, there is a long-term improvement in PMØ function compared with patients on conventional therapy. Better PMØ function suggests improved host defense status and may affect the peritoneum’s susceptibility to infection and potentially reduce the negative consequences of repeated intraperitoneal inflammation on long-term membrane function.

scholarly journals Long-Term Impact of COVID-19: A Systematic Review of the Literature and Meta-Analysis

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 900
Author(s):  
Diana C. Sanchez-Ramirez ◽  
Kaylene Normand ◽  
Yang Zhaoyun ◽  
Rodrigo Torres-Castro
Keyword(s):  
Quality Of Life ◽  
Lung Function ◽  
Functional Capacity ◽  
Post Infection ◽  
Respiratory Symptoms ◽  
Meta Analysis ◽  
Related Quality ◽  
Long Term Impact

Background: The long-term impact of COVID-19 is still unknown. This study aimed to explore post COVID-19 effects on patients chest computed tomography (CT), lung function, respiratory symptoms, fatigue, functional capacity, health-related quality of life (HRQoL), and the ability to return to work beyond 3 months post infection. Methods: A systematic search was performed on PubMed, Web of Science, and Ovid MEDLINE on 22 May 2021, to identify studies that reported persistent effects of COVID-19 beyond 3 months follow-up. Data on the proportion of patients who had the outcome were collected and analyzed using a one-group meta-analysis. Results: Data were extracted from 24 articles that presented information on a total of 5323 adults, post-infection, between 3 to 6 months after symptom onset or hospital discharge. The pooled prevalence of CT abnormalities was 59% (95% CI 44–73, I2 = 96%), abnormal lung function was 39% (95% CI 24–55, I2 = 94%), fatigue was 38% (95% CI 27–49, I2 = 98%), dyspnea was 32% (95% CI 24–40, I2 = 98%), chest paint/tightness was 16% (95% CI 12–21, I2 = 94%), and cough was 13%, (95% CI 9–17, I2 = 94%). Decreased functional capacity and HRQoL were found in 36% (95% CI 22–49, I2 = 97%) and 52% (95% CI 33–71, I2 = 94%), respectively. On average, 8 out of 10 of the patients had returned to work or reported no work impairment. Conclusion: Post-COVID-19 patients may experience persistent respiratory symptoms, fatigue, decreased functional capacity and decreased quality of life up to 6 months after infection. Further studies are needed to establish the extent to which post-COVID-19 effects continue beyond 6 months, how they interact with each other, and to clarify their causes and their effective management.

scholarly journals The Long-Term Effect of Exposure to Particulate Matter Air Pollution on the Incidence of Myocardial Infarction: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Masoud Khosravipour ◽  
Roya Safari-Faramani ◽  
Fatemeh Rajati ◽  
Fariborz Omidi
Keyword(s):  
Myocardial Infarction ◽  
Air Pollution ◽  
Particulate Matter ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Aerodynamic Diameter ◽  
Long Term Effect ◽  
Inverse Variance ◽  
Long Term Impact

Abstract This study systematically reviews the long-term impact of exposure to particulate matter (PM) air pollution with aerodynamic diameter ≤ 10 µm on the incidence of myocardial infarction (MI). The relevant databases were searched with appropriate keywords on February 29, 2020. A random-effects model through a generic inverse-variance method was used to calculate the pooled hazard ratio (HR) and 95% confidence interval (CI) of MI. The number of 17 cohort studies with more than 18 million participants and 800,000 cases of MI were included. A significantly higher risk of MI was observed per 1 µg/m3 increment of PM with aerodynamic diameter ≤ 10 µm (HR= 1.02,95 % CI = 1.01, 1.03). Subgroup analysis according to the study population indicates subjects with cardiovascular diseases history had a significantly greater risk of MI per 1 µg/m3 increase in PM with aerodynamic diameter ≤ 10 µm level (HR= 1.05,95% CI= 1.01, 1.08). Subgroup analysis according to aerodynamic diameter of PM showed only a significant stronger risk of MI per 1 µg/m3 increase in PM with aerodynamic diameter < 2.5 µm (HR= 1.01,95% CI= 1.00, 1.02). The pooled result confirms a significant association between the long-term exposure to PM air pollution and the developing of MI.

scholarly journals Long-term high-yield skeletal muscle stem cell expansion through staged perturbation of cytokine signaling in a soft hydrogel culture platform

2020 ◽  
Author(s):  
Alexander M. Loiben ◽  
Kun Ho Kim ◽  
Sharon Y. Soueid-Baumgarten ◽  
Victor M. Aguilar ◽  
Jonathan Chin Cheong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ex Vivo ◽  
High Yield ◽  
Muscle Stem Cell ◽  
Muscle Stem Cells ◽  
Stem Cell Expansion ◽  
Cytokine Cocktail ◽  
Tnf Α

AbstractMuscle stem cells (MuSCs) are an essential stem cell population for skeletal muscle homeostasis and regeneration throughout adulthood. MuSCs are an ideal candidate for cell therapies for chronic and acute muscle injuries and diseases given their inherent ability to self-renew and generate progenitor cells capable of myogenic commitment and fusion. Given their rarity and propensity to lose stem-cell potential in prolonged culture, methods for ex vivo MuSC expansion that achieve clinical-scale stem cell yields represent a critical unmet need in muscle cell-therapeutic development. Here, we tested a microenvironment engineering approach to achieve long-term adult mouse MuSC expansion suitable for clinical demands through the combined optimization of techniques previously reported to achieve small-yield MuSC expansion in short-term cultures. We developed an optimized protocol for high-yield MuSC expansion through the combination of inflammatory cytokine and growth factor co-stimulation, temporally-staged inhibition of the p38α/β mitogen activated protein kinase signaling pathway, and modulation of substrate rigidity in long-term hydrogel cultures. We found that, on soft, muscle-mimicking (12 kPa) hydrogel substrates, a mixture of the cytokines TNF-α, IL-1α, IL-13, and IFN-γ and the growth factor FGF2 stimulated robust exponential proliferation of adult MuSCs from both wildtype and mdx dystrophic mice for up to five weeks of culture that was accompanied by a phenotype shift towards committed myocytes. After observing that the temporal variation in myogenic commitment coincided with an oscillatory activation of p38α/β signaling, we tested a late-stage p38α/β inhibition strategy and found that blocking p38α/β signaling after three weeks, but not earlier, substantially enhanced cell yield, stem-cell phenotypes, and, critically, preserved transplantation potential for up to five weeks of FGF2/cytokine mix culture on soft hydrogels. Notably, this retention of transplant engraftment potency was not observed on traditional plastic substrates. We estimate that this protocol achieves >108-fold yield in Pax7+ stem cells from each starting MuSC, which represents a substantial improvement in stem-cell yield from long-term cultures compared to established methods.HighlightsTNF-α/IL-1α/IL-13/IFN-γ cytokine cocktail supports prolonged MuSC proliferation ex vivo but induces differentiation.Cytokine cocktail regulates cell signaling with varied prolonged activation signatures.Effects of p38α/β inhibition on cytokine-induced MuSC expansion are stage-dependent.Soft hydrogels with late-stage p38α/β inhibition expand functional Pax7+ MuSCs long-term.Short summaryCosgrove and colleagues develop a long-term muscle stem cell expansion protocol by combining a tunable stiffness hydrogel substrate, an inflammatory cytokine cocktail, and targeted inhibition of p38 MAPK signaling. They show that soft, muscle-mimicking hydrogels with delayed p38 inhibition yield robust quantities of Pax7+ functional muscle stem cells.

scholarly journals Grape-Seed Proanthocyanidins are Able to Reverse Intestinal Dysfunction and Metabolic Endotoxemia Induced by a Cafeteria Diet in Wistar Rats

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 979 ◽  
Author(s):  
Carlos González-Quilen ◽  
Katherine Gil-Cardoso ◽  
Iris Ginés ◽  
Raúl Beltrán-Debón ◽  
Montserrat Pinent ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Ex Vivo ◽  
Ussing Chamber ◽  
Intestinal Barrier ◽  
Grape Seed ◽  
Cafeteria Diet ◽  
Tnf Α ◽  
Obesogenic Diet ◽  
Metabolic Endotoxemia

We evaluated the effectiveness of pharmacological doses of grape-seed proanthocyanidin extract (GSPE) in reversing intestinal barrier alterations and local inflammation in female Wistar rats fed a long-term obesogenic diet. Animals were fed a 17-week cafeteria diet (CAF diet), supplemented with daily GSPE doses (100 or 500 mg kg−1 body weight) during the final two weeks. CAF diet enhanced the intestinal permeation of an orally administered marker (ovalbumin, OVA) and increased the plasma levels of tumor necrosis factor-α (TNF-α) and lipopolysaccharides (LPS) in 2–3-fold. Ex vivo Ussing chamber assays showed a 55–70% reduction in transepithelial electrical resistance (TEER) and increased the TNF-α secretions in both small and large intestinal sections with a 25-fold increment in the ileum. Ileal tissues also presented a 4-fold increase of myeloperoxidase (MPO) activity. Both GSPE-treatments were able to restitute TEER values in the ileum and colon and to reduce plasma LPS to basal levels without a dose-dependent effect. However, effects on the OVA permeation and TNF-α secretion were dose and section-specific. GSPE also reduced ileal MPO activity and upregulated claudin 1 gene expression. This study provides evidence of the efficacy of GSPE-supplementation ameliorating diet-induced intestinal dysfunction and metabolic endotoxemia when administered at the end of a long-term obesogenic diet.

scholarly journals Ex Vivo Kinetics of Early and Long-Term Multifunctional Human Leukocyte Antigen E-Specific CD8+ Cells in Volunteers Immunized with the Ty21a Typhoid Vaccine

2010 ◽  
Vol 17 (9) ◽  
pp. 1305-1314 ◽  
Author(s):  
Rosângela Salerno-Goncalves ◽  
Rezwanul Wahid ◽  
Marcelo B. Sztein
Keyword(s):  
T Cells ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Typhoid Vaccine ◽  
Tnf Α ◽  
Ifn Γ ◽  
Kinetics Of

ABSTRACT T cells are likely to play an important role in the host defense against Salmonella enterica serovar Typhi, the causative agent of typhoid fever. We have shown that HLA-E can function as a restriction element for S. Typhi-specific CD8+ T cells. Because of the potential importance of HLA-E-restricted CD8+ responses in resistance to Salmonella infection, we characterized these responses and investigated their kinetics of appearance and persistence in volunteers immunized orally with the licensed attenuated Ty21a strain typhoid vaccine. Cells were obtained from volunteers before and at days 2, 4, 7, 10, 14, 28, 42, 56, 120, 180, 360, and 720 after immunization. An ex vivo multicolor staining panel including antibodies to CD107a and -b, interleukin-2, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) was used to functionally assess memory T-cell subsets by flow cytometry. Increases in cytokine-secreting CD8+ cells were observed in the T effector/memory (TEM) and CD45RA+ TEM (TEMRA) subsets as early as 4 days after immunization and persisted, particularly in the TEMRA subset, up to 2 years after immunization. The majority of HLA-E-restricted CD8+ cells 28 to 56 days after immunization coexpressed CD107, IFN-γ, and TNF-α, showing characteristic features of multifunctional T cells. In summary, the multifunctionality and longevity of the HLA-E-restricted CD8 responses observed in this study highlight their significance in adaptive immunity to S. Typhi. Finally, this is the first demonstration, in either animals or humans, of the presence of long-term multifunctional HLA-E-restricted CD8+ cells after immunization.

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

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