Particle-Induced Pulmonary Acute Phase Response Correlates with Neutrophil Influx Linking Inhaled Particles and Cardiovascular Risk

Background

Particulate air pollution is associated with cardiovascular disease. Acute phase response is causally linked to cardiovascular disease. Here, we propose that particle-induced pulmonary acute phase response provides an underlying mechanism for particle-induced cardiovascular risk.

Methods

We analysed the mRNA expression of Serum Amyloid A (Saa3) in lung tissue from female C57BL/6J mice exposed to different particles including nanomaterials (carbon black and titanium dioxide nanoparticles, multi- and single walled carbon nanotubes), diesel exhaust particles and airborne dust collected at a biofuel plant. Mice were exposed to single or multiple doses of particles by inhalation or intratracheal instillation and pulmonary mRNA expression of Saa3 was determined at different time points of up to 4 weeks after exposure. Also hepatic mRNA expression of Saa3, SAA3 protein levels in broncheoalveolar lavage fluid and in plasma and high density lipoprotein levels in plasma were determined in mice exposed to multiwalled carbon nanotubes.

Results

Pulmonary exposure to particles strongly increased Saa3 mRNA levels in lung tissue and elevated SAA3 protein levels in broncheoalveolar lavage fluid and plasma, whereas hepatic Saa3 levels were much less affected. Pulmonary Saa3 expression correlated with the number of neutrophils in BAL across different dosing regimens, doses and time points.

Conclusions

Pulmonary acute phase response may constitute a direct link between particle inhalation and risk of cardiovascular disease. We propose that the particle-induced pulmonary acute phase response may predict risk for cardiovascular disease.     

Exposure to an organometal compound stimulates adipokine and cytokine expression in white adipose tissue

ObjectiveWhite adipose tissue (WAT) is now considered a defined tissue capable of interactions with other organ systems. WAT role in elevating the level of systemic chronic inflammation suggests that alterations in this tissue as the result of disease or environmental factors may influence the development and progression of various obesity-related pathologies. This study investigated WAT cell-specific responses to an organometal compound, trimethyltin (TMT), to determine possible contribution to induced inflammation.MethodsHuman primary mature adipocytes and macrophage differentiated THP-1 cells were cultured in TMT presence and relative toxicities and different adipokine levels were determined. The inflammatory response was examined in TMT presence for primary cells from obese ob/ob mice WAT, and after TMT injection in ob/ob mice.ResultsBoth adipocytes and macrophages were resistant to cell death induced by TMT. However, adipocytes cultured in TMT presence showed increased expression of TNFα and IL-6, and modified leptin levels. In macrophage cultures, TMT also increased TNFα and IL-6, while MCP-1 and MIP-1α were decreased. In vivo, a single injection of TMT in ob/ob mice, elevated TNFα, MIP-1α and adiponectin in WAT.ConclusionsElevation of the inflammatory related products can be induced by chemical exposure in adipocytes and macrophages, as well as murine WAT. These data suggest that numerous factors, including a systemic chemical exposure, can induce an inflammatory response from the WAT. Furthermore, when characterizing both chemical-induced toxicity and the progression of the chronic inflammation associated with elevated WAT content, such responses in this target tissue should be taken into consideration.     

大气细颗粒污染物 PM2.5 浓度及对肺上皮细胞炎性因子的影响

目的:研究大气细颗粒污染物(PM2.5)浓度及对肺上皮细胞(A549细胞)炎性因子的影响。方法:测定2013年1月至2013年12月北京市某城区PM2.5浓度,比较不同PM2.5浓度对A549细胞炎性因子IL-6、TNF-α表达水平的影响。结果:北京市细颗粒污染物PM2.5日均值春季、夏季、秋季、冬季分别为174.3μg/m3、143.5μg/m3、166.7μg/m3、189.6μg/m3,四季超标率差异无统计学意义(P>0.05);大气细颗粒污染物PM2.5对肺上皮细胞IL-6、TNF-α的影响,春季、夏季、秋季、冬季四季之间差异无统计学意义(P>0.05);随着PM2.5浓度升高IL-6、TNF-α表达水平升高,差异有统计学意义(P<0.05);随着染毒时间延长IL-6、TNF-α表达水平升高,差异有统计学意义(P<0.05)。结论:大气细颗粒污染物浓度升高会使肺上皮细胞炎性因子表达增强。     

The effect of long-term exposures to hypersaline particles originated from drying Urmia hypersaline Lake on the increased cardiovascular risks in the villagers around the Lake

Abstract

Background and Objectives: The world’s second largest permanent hypersaline lake, Lake Urmia, is drying in recent years and the dried bed of the Lake acts as a hypersaline particle emission source. Therefore, we aim to evaluate (for the first time to our knowledge) the association between hypersaline particles and biomarkers of inflammation and coagulation (hs-CRP and fibrinogen) in the residents around the Lake Urmia.

Methods: Three regions were selected as clean (region No.1) and polluted regions (region No.2 and No.3) for ambient particulate matter around the Urmia Lake from 2008 to 2015. In order to confirm the selected regions concentration of APM was measured in the selected regions for six months. Totally 123 participants were selected randomly, fibrinogen, hs-CRP and covariates were measured in the selected regions and were analyzed using multiple linear regression models.

Results: We found a statistically significant association between the hypersaline particles and fibrinogen in both polluted regions. This is while an association between hypersaline particles and hs-CRP was significant only in the polluted region No.2.

Conclusions: These results are consistent with our hypothesis that long-term exposure to hypersaline particles originated from drying Urmia hypersaline Lake is related to increased levels of hs-CRP and fibrinogen.     

Induction of pulmonary matrilysin expression by combustion and ambient air particles

The molecular mechanism(s) by which chemically complex air pollution particles mediate their adverse health effects is not known. We have examined the ability of combustion and ambient air particles to induce pulmonary matrilysin expression due to the well-documented role of matrix metalloproteinases in tissue injury and repair responses. Rats were exposed to saline, residual oil fly ash (2.5 mg/rat), or ambient air particles (2.5 mg/rat) via intratracheal instillation and examined 3-72 h after exposure. Saline-exposed animals had low levels of matrilysin mRNA, whereas the animals exposed to either complex particle showed an early induction of pulmonary matrilysin gene expression as well as of the 19-kDa activated form of matrilysin. Immunocytochemistry and in situ hybridization analyses identified the alveolar macrophages and monocytes as primary sources of air pollution particle-induced matrilysin expression. Matrilysin gene induction and protein activation by combustion and ambient air particles correlated with the early histopathological changes produced by these particles. These results demonstrate the ability of combustion and ambient air particles to induce pulmonary matrilysin expression and suggest a role for this matrix metalloproteinase in the initiation of lung injury produced by these particles.     

Particulate matter exposure induces persistent lung inflammation and endothelial dysfunction

Epidemiologic and animal studies have shown that exposure to particulate matter air pollution (PM) is a risk factor for the development of atherosclerosis. Whether PM-induced lung and systemic inflammation is involved in this process is not clear. We hypothesized that PM exposure causes lung and systemic inflammation, which in turn leads to vascular endothelial dysfunction, a key step in the initiation and progression of atherosclerosis. New Zealand White rabbits were exposed for 5 days (acute, total dose 8 mg) and 4 wk (chronic, total dose 16 mg) to either PM smaller than 10 mum (PM(10)) or saline intratracheally. Lung inflammation was quantified by morphometry; systemic inflammation was assessed by white blood cell and platelet counts and serum interleukin (IL)-6, nitric oxide, and endothelin levels. Endothelial dysfunction was assessed by vascular response to acetylcholine (ACh) and sodium nitroprusside (SNP). PM(10) exposure increased lung macrophages (P<0.02), macrophages containing particles (P<0.001), and activated macrophages (P<0.006). PM(10) increased serum IL-6 levels in the first 2 wk of exposure (P<0.05) but not in weeks 3 or 4. PM(10) exposure reduced ACh-related relaxation of the carotid artery with both acute and chronic exposure, with no effect on SNP-induced vasodilatation. Serum IL-6 levels correlated with macrophages containing particles (P=0.043) and ACh-induced vasodilatation (P=0.014 at week 1, P=0.021 at week 2). Exposure to PM(10) caused lung and systemic inflammation that were both associated with vascular endothelial dysfunction. This suggests that PM-induced lung and systemic inflammatory responses contribute to the adverse vascular events associated with exposure to air pollution.     

Effects of ambient air particles on the endothelin system in human pulmonary epithelial cells (A549)

Inhalation of urban particles results in higher circulating levels of the vasoconstrictor peptide endothelin-1 (ET-1), which may account for the adverse cardiovascular impacts associated with air pollution. The objective of this study was to examine the direct effects of urban particles on the production of ET-1 by human epithelial cells (A549). A549 cells were exposed to TiO₂, SiO₂, Ottawa urban particulate matter EHC-93, and fractions of the urban particles. The levels of ET-1, interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) in the culture medium were detected by ELISA. The mRNA levels of preproET-1, endothelin converting enzyme (ECE-1), ETa receptor and ETb receptor, matrix metalloproteinase (MMP-2), tissue inhibitor of MMP (TIMP-2), and heat shock protein (HSP-70) were determined by quantitative real-time RT-PCR. Cluster analysis of the variables identified similarities in the patterns of effects. Cluster I comprised variables that were primarily inhibited by particles: ET-1 and MMP-2 mRNAs, ET-1 and bigET-1 peptides, and cell viability. Clusters II and III comprised variables that were either inhibited or induced, depending on the test material: HSP-70, ETaR and ECE mRNAs, and IL-8 and VEGF proteins. Cluster IV comprised variables that were mainly induced by particle preparations: ETbR and TIMP-2 mRNAs. The decreased expression of preproET-1 in A549 cells suggests that epithelial cells may not be the source of higher pulmonary ET-1 spillover in the circulation measured in vivo in response to inhaled urban particles. However, higher ECE-1 in A549 cells after exposure to particles suggests an increased ability to process bigET-1 into the mature ET-1 peptide, while increased receptor expression implies higher responsiveness. The increased release of IL-8 and VEGF by epithelial cells in response to particles could possibly upregulate ET-1 production in the adjacent pulmonary capillary endothelial cells, with concomitant increased ET-1 spillover in the systemic circulation.     

Acute Inflammatory Responses of Nanoparticles in an Intra-Tracheal Instillation Rat Model

Exposure to hard metal tungsten carbide cobalt (WC-Co) “dusts” in enclosed industrial environments is known to contribute to the development of hard metal lung disease and an increased risk for lung cancer. Currently, the influence of local and systemic inflammation on disease progression following WC-Co exposure remains unclear. To better understand the relationship between WC-Co nanoparticle (NP) exposure and its resultant effects, the acute local pulmonary and systemic inflammatory responses caused by WC-Co NPs were explored using an intra-tracheal instillation (IT) model and compared to those of CeO₂ (another occupational hazard) NP exposure. Sprague-Dawley rats were given an IT dose (0-500 μg per rat) of WC-Co or CeO₂ NPs. Following 24-hr exposure, broncho-alveolar lavage fluid and whole blood were collected and analyzed. A consistent lack of acute local pulmonary inflammation was observed in terms of the broncho-alveolar lavage fluid parameters examined (i.e. LDH, albumin, and macrophage activation) in animals exposed to WC-Co NP; however, significant acute pulmonary inflammation was observed in the CeO₂ NP group. The lack of acute inflammation following WC-Co NP exposure contrasts with earlier in vivo reports regarding WC-Co toxicity in rats, illuminating the critical role of NP dose and exposure time and bringing into question the potential role of impurities in particle samples. Further, we demonstrated that WC-Co NP exposure does not induce acute systemic effects since no significant increase in circulating inflammatory cytokines were observed. Taken together, the results of this in vivo study illustrate the distinct differences in acute local pulmonary and systemic inflammatory responses to NPs composed of WC-Co and CeO₂; therefore, it is important that the outcomes of pulmonary exposure to one type of NPs may not be implicitly extrapolated to other types of NPs.     

Fetuin-A and Albumin Alter Cytotoxic Effects of Calcium Phosphate Nanoparticles on Human Vascular Smooth Muscle Cells

Calcification is a detrimental process in vascular ageing and in diseases such as atherosclerosis and arthritis. In particular, small calcium phosphate (CaP) crystal deposits are associated with inflammation and atherosclerotic plaque de-stabilisation. We previously reported that CaP particles caused human vascular smooth muscle cell (VSMC) death and that serum reduced the toxic effects of the particles. Here, we found that the serum proteins fetuin-A and albumin (≥1 µM) reduced intracellular Ca²⁺ elevations and cell death in VSMCs in response to CaP particles. In addition, CaP particles functionalised with fetuin-A, but not albumin, were less toxic than naked CaP particles. Electron microscopic studies revealed that CaP particles were internalised in different ways; via macropinocytosis, membrane invagination or plasma membrane damage, which occurred within 10 minutes of exposure to particles. However, cell death did not occur until approximately 30 minutes, suggesting that plasma membrane repair and survival mechanisms were activated. In the presence of fetuin-A, CaP particle-induced damage was inhibited and CaP/plasma membrane interactions and particle uptake were delayed. Fetuin-A also reduced dissolution of CaP particles under acidic conditions, which may contribute to its cytoprotective effects after CaP particle exposure to VSMCs. These studies are particularly relevant to the calcification observed in blood vessels in patients with kidney disease, where circulating levels of fetuin-A and albumin are low, and in pathological situations where CaP crystal formation outweighs calcification-inhibitory mechanisms.     

Ambient source-specific particles are associated with prolonged repolarization and increased levels of inflammation in male coronary artery disease patients

Ambient particulate air pollution has been associated with altered cardiac function and systemic inflammation. We reported repolarization changes and variations in markers of inflammation in association with ambient particulate exposure in a panel of male coronary artery disease (CAD) patients. The objective of this analysis was to identify the specific sources associated with these effects. A panel of male CAD patients participated in 12 clinical visits in Erfurt, Germany. We used 56 patients' 5min ECG recordings for the analysis of repolarization parameters QT interval and T wave amplitude, and 57 patients' plasma samples to determine the biomarkers von Willebrand factor (vWF) and C-reactive protein (CRP). Linear and logistic regression models were used to analyze the associations between five particle source factors (airborne soil, local traffic-related ultrafine particles, combustion-generated aerosols, diesel traffic-related particles, and secondary aerosols) and these health parameters adjusting for trend, weekday and meteorological variables. An increase in QT interval and a decrease in T wave amplitude were observed in association with traffic-related particles exposure during 0-23h before the ECG recordings. The inflammatory marker vWF increased in association with both traffic-related particles and combustion-generated aerosols at different exposure lags. All source particles had positive associations with CRP levels above the 90th percentile (8.5mg/l). These results suggest that traffic-related and combustion-generated particles show stronger adverse health impact with regard to cardiac effects, and that particles from different sources induce an acute phase response in these patients.     

Dynamic differences in dietary polyunsaturated fatty acid metabolism in sputum of COPD patients and controls

IntroductionDisturbances in onset and resolution of inflammation in chronic obstructive pulmonary disease (COPD) are incompletely understood. Dietary polyunsaturated fatty acids (PUFAs) can be converted into lipid mediators here collectively named oxylipins. These include classical eicosanoids, but also pro-resolving mediators. A balanced production of pro-inflammatory and pro-resolving oxylipins is of importance for adequate inflammatory responses and subsequent return to homeostasis.ObjectivesHere we investigated if PUFA metabolism is disturbed in COPD patients.MethodsFree PUFA and oxylipin levels were measured in induced sputum samples from the Bergen COPD cohort and COPD exacerbation study using liquid chromatography-mass spectrometry. Additionally, effects of whole cigarette smoke on PUFA metabolism in air-liquid interface cultures of primary bronchial epithelial cells were assessed.ResultsSignificantly lower levels of free alpha-linolenic acid, linoleic acid and eicosapentaenoic acid (EPA) were detected in sputum from stable COPD patients compared to controls. During acute exacerbation (AE), levels of free arachidonic acid and docosapentaenoic acid were higher than in stable COPD patients. Furthermore, levels of omega-3 EPA- and docosahexaenoic acid-derived oxylipins were lower in sputum from stable COPD patients compared to controls. Cyclooxygenase-2-converted mediators were mostly increased during AE. In vitro studies additionally showed that cigarette smoke exposure may also directly contribute to altered epithelial PUFA metabolism, and indirectly by causing airway epithelial remodelling.ConclusionsOur findings show significant differences in PUFA metabolism in COPD patients compared to controls, further changed during AE. Airway epithelial remodelling may contribute to these changes. These findings provide new insight in impaired inflammatory resolution in COPD.     

Omega-3 fatty acids are related to abnormal emotion processing in adolescent boys with attention deficit hyperactivity disorder

BackgroundIn addition to the core symptoms, attention deficit hyperactivity disorder (ADHD) is associated with poor emotion regulation. There is some evidence that children and young adults with ADHD have lower omega-3 levels and that supplementation with omega-3 can improve both ADHD and affective symptoms. We therefore investigated differences between ADHD and non-ADHD children in omega-3/6 fatty acid plasma levels and the relationship between those indices and emotion-elicited event-related potentials (ERPs).MethodsChildren/adolescents with (n=31) and without ADHD (n=32) were compared in their plasma omega-3/6 indices and corresponding ERPs during an emotion processing task.ResultsChildren with ADHD had lower mean omega-3/6 and ERP abnormalities in emotion processing, independent of emotional valence relative to control children. ERP abnormalities were significantly associated with lower omega-3 levels in the ADHD group.ConclusionsThe findings reveal for the first time that lower omega-3 fatty acids are associated with impaired emotion processing in ADHD children.     

Omega-3 fatty acid supplementation decreases matrix metalloproteinase-9 production in relapsing-remitting multiple sclerosis,

ObjectivesThe primary objective was to evaluate the effect of omega-3 fatty acids (omega-3 FA) on matrix metalloproteinase-9 (MMP-9) production by immune cells in multiple sclerosis (MS). Quality of life, fatty acid levels, and safety were also evaluated.Materials and MethodsTen participants with relapsing-remitting MS (RRMS) received omega-3 FA supplementation (9.6 g/day fish oil) in an open-label study. Participants were evaluated at four time points, baseline, after 1 month of omega-3 FA supplementation, after 3 months of omega-3 FA supplementation, and after a 3-month wash out.ResultsImmune cell secretion of MMP-9 decreased by 58% after 3 months of omega-3 FA supplementation when compared with baseline levels (p<0.01). This effect was coupled with a significant increase in omega-3 FA levels in red blood cell membranes.ConclusionsOmega-3 FA significantly decreased MMP-9 levels in RRMS and may act as an immune-modulator that has potential therapeutic benefit in MS patients.     

Pulmonary exposure to diesel exhaust particles enhances coagulatory disturbance with endothelial damage and systemic inflammation related to lung inflammation

Pulmonary exposure to diesel exhaust particles (DEP) enhances lung inflammation related to bacterial endotoxin (lipopolysaccharide [LPS]) in mice. Severe lung inflammation can reportedly induce coagulatory abnormalities and systemic inflammation. This study examined the effects of components of DEP on lung inflammation, pulmonary permeability, coagulatory changes, systemic inflammatory response, and lung-to-systemic translocation of LPS in a murine model of lung inflammation. ICR mice were divided into six experimental groups that intratracheally received vehicle, LPS (2.5 mg/kg), organic chemicals in DEP (DEP-OC; 4 mg/kg) extracted with dicloromethane), residual carbonaceous nuclei of DEP (washed DEP: 4 mg/kg), DEP-OC + LPS, or washed DEP + LPS. Both DEP components exacerbated lung inflammation, vascular permeability, and the increased fibrinogen and E-selectin levels induced by LPS. With overall trends, the exacerbation was more prominent with washed DEP than with DEP-OC. Washed DEP + LPS significantly decreased activated protein C and antithrombin-III and elevated circulatory levels of interleukin (IL)-6, keratinocyte chemoattractant (KC), and LPS as compared with LPS alone, whereas DEP-OC + LPS elevated IL-6, KC, and LPS without significance. These results show that DEP components, especially washed DEP, amplify the effects if LPS on the respiratory system and suggest that they contribute to the adverse health effects of particulate air pollution on the sensitive populations with predisposing vascular and/or pulmonary diseases, including ischemic vascular diseases and respiratory infection.     

Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women

ContextObesity is associated with insulin-resistance (IR), the key feature of type 2 diabetes. Although chronic low-grade inflammation has been identified as a central effector of IR development, it has never been investigated simultaneously at systemic level and locally in skeletal muscle and adipose tissue in obese humans characterized for their insulin sensitivity.ObjectivesWe compared metabolic parameters and inflammation at systemic and tissue levels in normal-weight and obese subjects with different insulin sensitivity to better understand the mechanisms involved in IR development.Methods30 post-menopausal women were classified as normal-weight insulin-sensitive (controls, CT) and obese (grade I) insulin-sensitive (OIS) or insulin-resistant (OIR) according to their body mass index and homeostasis model assessment of IR index. They underwent a hyperinsulinemic-euglycemic clamp, blood sampling, skeletal muscle and subcutaneous adipose tissue biopsies, an activity questionnaire and a self-administrated dietary recall. We analyzed insulin sensitivity, inflammation and IR-related parameters at the systemic level. In tissues, insulin response was assessed by P-Akt/Akt expression and inflammation by macrophage infiltration as well as cytokines and IκBα expression.ResultsSystemic levels of lipids, adipokines, inflammatory cytokines, and lipopolysaccharides were equivalent between OIS and OIR subjects. In subcutaneous adipose tissue, the number of anti-inflammatory macrophages was higher in OIR than in CT and OIS and was associated with higher IL-6 level. Insulin induced Akt phosphorylation to the same extent in CT, OIS and OIR. In skeletal muscle, we could not detect any inflammation even though IκBα expression was lower in OIR compared to CT. However, while P-Akt/Akt level increased following insulin stimulation in CT and OIS, it remained unchanged in OIR.ConclusionOur results show that systemic IR occurs without any change in systemic and tissues inflammation. We identified a muscle defect in insulin response as an early mechanism of IR development in grade I obese post-menopausal women.     

A high docosahexaenoic acid diet alters lung inflammation and recovery following repetitive exposure to aqueous organic dust extracts

Agricultural workers, especially those who work in swine confinement facilities, are at increased risk for developing pulmonary diseases including asthma, chronic obstructive pulmonary disease, and chronic bronchitis due to exposures to fumes, vapors, and organic dust. Repetitive exposure to agricultural dust leads to unresolved inflammation, a common underlying mechanism that worsens lung disease. Besides occupational exposure to dusts, diet also significantly contributes to inflammation and disease progression. Since DHA (docosahexaenoic acid), a polyunsaturated omega-3 fatty acid and its bioactive metabolites have key roles in inflammation resolution, we rationalized that individuals chronically exposed to organic dusts can benefit from dietary modifications. Here, we evaluated the role of DHA in modifying airway inflammation in a murine model of repetitive exposure to an aqueous extract of agricultural dust (three-week exposure to swine confinement dust extract, HDE) and after a one-week resolution/recovery period. We found that mice fed a high DHA diet had significantly increased bronchoalveolar lavage fluid (BALF) levels of DHA-derived resolvins and lower TNFα along with altered plasma levels of endocannabinoids and related lipid mediators. Following the one-week recovery we identified significantly reduced BALF cellularity and cytokine/chemokine release along with increased BALF amphiregulin and resolvins in DHA diet-fed versus control diet-fed mice challenged with HDE. We further report observations on the effects of repetitive HDE exposure on lung Ym1+ and Arg-1+ macrophages. Overall, our findings support a protective role for DHA and identify DHA-derived resolvins and endocannabinoids among the potential mediators of DHA in altering airway inflammation in chronic agricultural dust exposure.     

Immunomodulatory activity of brown algae Turbinaria ornata derived sulfated polysaccharide on LPS induced systemic inflammation

BackgroundInflammation and oxidative stress are common pathologies in a wide range of chronic diseases. Polysaccharides are known to exhibit antioxidant and anti-inflammatory potential and are suggested to possess immunomodulatory potential.PurposeHerein, the immunomodulatory activity of a sulfated polysaccharide (PS) separated from a brown marine algae Turbinaria ornata is studied in LPS instigated systemic inflammation in experimental rats.Study design and methodsMale SD rats are pretreated with different doses of PS (2.5, 5, 10 mg/kg bw) for a week followed by inducing systemic inflammation using LPS (10 mg/kg i.p.). Blood withdrawn after 8 h of LPS injection is subjected to hematological analysis (WBC, HCT, and PLT). After 24 h of LPS induction, cardiac tissue was isolated and subjected to biochemical, molecular, and histopathological analysis. Effect of PS pre-treatment (2.5, 5, 10 mg/kg bw) was checked by assessing serum parameters (AST, CK-MB, and γGT), antioxidant markers (LPO, GSH, SOD, Grx) and inflammatory markers (IL1β, IL6, IL10, NFκB), followed by analyzing the iNOS, PI3k and Akt to identify the probable mode of action.ResultsElevated levels of AST, CK-MB, and γGT in serum were significantly reduced on PS pretreatment. LPS significantly raised the LPO and Grx levels in heart tissue whereas, PS pre-treatment significantly reduced LPO and Grx levels. GSH and SOD levels were reduced upon LPS induction and were brought to near normal by HD of PS. PS also reduced the mRNA levels of IL6, Trx, and increased IL10 levels in the heart tissue substantiating its anti-inflammatory and antioxidant potency. Further, IL1β, NFκB, iNOS, and pPI3k/pAkt expressions were significantly modulated by PS in the cardiac tissue substantiating the immunomodulatory effect. A trend of improvement in the inflammatory pathology was also observed in the heart tissue compared to LPS control, as confirmed by histopathology analysis.ConclusionAltogether, this study concludes the immunomodulatory potential of PS from the marine macroalgae Turbinaria ornata significantly and prevents LPS induced systemic inflammation in the cardiac tissue presumably influenced by the glucopyranose and fucopyranose subunits in the polysaccharide.     

Reduced alveolar macrophage migration induced by acute ambient particle (PM<Subscript>10</Subscript>) exposure

Increased levels of particulate air pollution (PM₁₀) have been implicated as a causal agent in pulmonary disease exacerbation and increased deaths from respiratory and cardiovascular disorders. The exact mechanism by which PM₁₀ drives toxicity in the lung is still unknown, but studies have focused on inhibition of macrophage function and impaired alveolar clearance mechanisms. To assess the effects of PM₁₀ on pulmonary macrophage clearance mechanisms ex vivo, Wistar rats were instilled with 125 or 250 μg of PM₁₀ collected from the North Kensington, London. Control rats were instilled with sterile saline. The rats were sacrificed after 18 h and a bronchoalveolar lavage (BAL) was performed. Macrophages isolated from the BAL fluid were assessed for ability to migrate towards a positive chemoattractant (ZAS) ex vivo and to perform phagocytosis. Macrophages isolated from the PM₁₀-exposed rats showed inhibition of potential to migrate. Macrophage phagocytic ability ex vivo was also significantly reduced by the presence of PM₁₀ inside the cells. This study indicates that acute PM₁₀ exposure diminishes macrophage motility and phagocytosis in a manner that could prove deleterious to particle clearance from the alveolar region of the lung. Decreased particle clearance promotes inflammation, and hence, warrants further investigation in relation to the effects of chronic PM₁₀ exposure on macrophage clearance mechanisms and establishing the mechanisms behind decreased macrophage migration.     

The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles

Ambient particulate matter (PM) is an environmental factor that has been associated with increased respiratory morbidity and mortality. The major effect of ambient PM on the pulmonary system is the exacerbation of inflammation, especially in susceptible people. One of the mechanisms by which ambient PM exerts its proinflammatory effects is the generation of oxidative stress by its chemical compounds and metals. Cellular responses to PM-induced oxidative stress include activation of antioxidant defense, inflammation, and toxicity. The proinflammatory effect of PM in the lung is characterized by increased cytokine/chemokine production and adhesion molecule expression. Moreover, there is evidence that ambient PM can act as an adjuvant for allergic sensitization, which raises the possibility that long-term PM exposure may lead to increased prevalence of asthma. In addition to ambient PM, rapid expansion of nanotechnology has introduced the potential that engineered nanoparticles (NP) may also become airborne and may contribute to pulmonary diseases by novel mechanisms that could include oxidant injury. Currently, little is known about the potential adverse health effects of these particles. In this communication, the mechanisms by which particulate pollutants, including ambient PM and engineered NP, exert their adverse effects through the generation of oxidative stress and the impacts of oxidant injury in the respiratory tract will be reviewed. The importance of cellular antioxidant and detoxification pathways in protecting against particle-induced lung damage will also be discussed.