Clinical Research Progress of Peripheral Blood Eosinophils in Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease(COPD)accounts for one of the major health and economic burdens worldwide.As a heterogeneous disease,the underlying inflammatory pattern of COPD differs from the previously thought neutrophil-dominated inflammation,with eosinophilic inflammation occupying approximately one third of stable COPD.Although the eosinophil(EOS)threshold associated with clinical relevance in patients with COPD is currently debated,eosinophil count can be used as a biomarker to guide treatment and to assess the risk of acute exacerbations of COPD,the efficacy of inhaled corticosteroids,and clinical outcomes.The purpose of this review is to describe the biological characteristics of eosinophils and the related research progress as clinical biomarkers.

Diagnostic role of fractional exhaled nitric oxide in pediatric eosinophilic esophagitis, relationship with gastric and duodenal eosinophils

BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.

Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders

Eosinophils are currently regarded as versatile mobile cells controlling and regulating multiple biological pathways and responses in health and disease.These cells store in their specific granules numerous biologically active substances(cytotoxic cationic proteins, cytokines, growth factors, chemokines,enzymes) ready for rapid release. The human gut is the main destination of eosinophils that are produced and matured in the bone marrow and then transferred to target tissues through the circulation. In health the most important functions of gut-residing eosinophils comprise their participation in the maintenance of the protective mucosal barrier and interactions with other immune cells in providing immunity to microbiota of the gut lumen. Eosinophils are closely involved in the development of inflammatory bowel disease(IBD),when their cytotoxic granule proteins cause damage to host tissues. However,their roles in Crohn’s disease and ulcerative colitis appear to follow different immune response patterns. Eosinophils in IBD are especially important in altering the structure and protective functions of the mucosal barrier and modulating massive neutrophil influx to the lamina propria followed by transepithelial migration to colorectal mucus. IBD-associated inflammatory process involving eosinophils then appears to expand to the mucus overlaying the internal gut surface. The author hypothesises that immune responses within colorectal mucus as well as ETosis exerted by both neutrophils and eosinophils on the both sides of the colonic epithelial barrier act as additional pathogenetic factors in IBD. Literature analysis also shows an association between elevated eosinophil levels and better colorectal cancer(CRC) prognosis, but mechanisms behind this effect remain to be elucidated. In conclusion, the author emphasises the importance of investigating colorectal mucus in IBD and CRC patients as a previously unexplored milieu of disease-related inflammatory responses.

Blood eosinophils and mortality in patients with acute respiratory distress syndrome: A propensity score matching analysis

BACKGROUND: The effect of blood eosinophils(EOSs) on mortality in acute respiratory distress syndrome(ARDS) patients and whether corticosteroids affect this effect are unclear.METHODS: The Medical Information Mart for Intensive Care III database(version 1.4) was used to extract data. Patients with ARDS were selected for inclusion. Cox regression models using the backward stepwise method and propensity score matching(PSM) were used to assess the relationship between blood EOS counts and 28-day mortality. RESULTS: A total of 2,567 patients with ARDS were included, and the 28-day mortality rate was 24.19%. The crude 28-day mortality was significantly lower in patients with EOS counts ≥2%(18.60% [85/457] vs. 25.40% [536/2,110], P=0.002) than in those with EOS counts <2%. In the Cox regression model, the EOS counts ≥2% showed a significant association with the decreased 28-day mortality(hazard ratio [HR] 0.731;95% confidence interval [95% CI] 0.581–0.921, P=0.008). In the corticosteroid non-use subgroup, EOS counts ≥2% was significantly related to decreased 28-day mortality(HR 0.697, 95% CI 0.535–0.909, P=0.008), but the result was not significant in the corticosteroid non-use subgroup model(P=0.860). A total of 457 well-matched pairs were obtained by a 1:1 matching algorithm after PSM. The 28-day mortality remained significantly lower in the EOS counts ≥2% group(18.60% [85/457] vs. 26.70% [122/457], P=0.003).CONCLUSIONS Higher EOS counts are related to lower 28-day mortality in ARDS patients, and this relationship can be counteracted by using corticosteroids.

Eosinophils and mast cells as therapeutic targets in pediatric functional dyspepsia

There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia(FD).Importantly,inflammation may serve as a mediator between psychologic and physiologic functions.This manuscript reviews the literature implicating two inflammatory cell types,mast cells and eosinophils,in the generation of dyspeptic symptoms and explores their potential as targets for the treatment of FD.There are a number of inciting events which may initiate an inflammatory response,and the subsequent recruitment and activation of mast cells and eosinophils.These include internal triggers such as stress and anxiety,as well as external triggers such as microbes and allergens.Previous studies suggest that there may be efficacy in utilizing medications directed at mast cells and eosinophils.Evidence exists to suggest that combining "anti-inflammatory" medications with other treatments targeting stress can improve the rate of symptom resolution in pediatric FD.

The role of eosinophils in asthma

Asthma is a chronic inflammatory disorder of the airways characterized by recurring episodes of reversible airway obstruction, hyper-responsiveness, wheezing, breathlessness and coughing. Clinical diagnosis of asthma is based on the pattern of clinical symptoms and pulmonary fuction tests. Asthma affectes 5% - 10% of the population and the number of worldwide cases is approximately 300 milliones. The incidence of this disease is increasing particulry in western countries [1]. It is the cause of a huge economic burden to national healthcare services. In a minority of cases, asthma is potentially fatal. After a period when fatalities appeared to be increasing [2], in recent years asthma-related mortality has progressively declined due to the develop- ment of specific asthma disease management programs, as well as the extensive use of in- haled corticosteroids [3]. Inflammation of the airways is a central component in asthma. In- flammation is associated with infliltration of the airway wall with eosinophiles and or neutron- philes mast cell degranulation and T cell active- tion. Other pathological features include, sub- basement membrane thickening, loss of epithet- lial cell integrity, goblet cells hyperplasia In- crease in airway smooth muscle mass. Eosino- phils are thought to be vital in the development of airway hyperreactivity, with the eosinophil cationic protein playing a crucial role [4]. The fact that treatment of asthma with corticos-teroids reduces eosinophils numbers and decreases airway reactivity further supports this hypothesis.

Effect of RNA interference therapy on the mice eosinophils CCR3 gene and granule protein in the murine model of allergic rhinitis

Objective:To observe the clinical manifestations of allergic rhinitis mice and the expression changes of the eosinophils CCR3 and the granule protein rnRNA in the bone marrow,peripheral blood and nasal lavage fluid.Mctliods:Twenty-four BALB/c mice were randomly divided into the control group.PBS therapy group.siKNA therapy group and the CCR3 siRNA therapy group(n=6).Allergic rhinitis model were sensitized and stimulated by ovalbunfin,and CCR3 siKNA therapy group were administered with CCH3 transnasally before stimulated.The levels of the eosinophils CCR3.MBP.ECP and EPO in bone marrow,peripheral blood and nasal lavage fluid were detected by RT-PCR.Results:Compared to the control group and CCR3 siR.NA therapy group,the nasal mucosa of the PBS therapy group and siRNA therapy group developed epithalaxy.goblet cells hyperplasia,squamous epithelium metaplasia,epithelium necrosis,lamina propria and submucosa gland hyperplasia,vasodilatation,tissue edema,and the characterized eosinophil infiltration.RT-PCR indicated that the CCR3 rnRNA,MBP.ECP and EPC)expression in bone marrow,peripheral blood and nasal lavage fluid of the CCR3 siKNA therapy group was lower than the PBS therapy group and siR.NA therapy group(P<0.05).Conclusions:The RNA interference therapy to CCR3 by local administration pernasal can suppress the process of the development,migration and invasion of the allergic rhinitis eosinophil,thus can reduce the effect of eosinophils and then reduce the inflammation effect of the allergic rhinitis.It may be a new treatment for respiratory tract allergic inflammation.

Arterial and venous thromboembolism risk associated with blood eosinophils: A systematic review and meta-analysis

The association between blood eosinophil(EOS)counts and arterial/venous throm-bosis is unclear.We aim to explore whether EOS count is a risk factor for throm-bosis.We searched several databases and preprint platforms using core terms‘eosinophil’,‘myocardial infarction’,‘ischemic stroke’,and‘venous thromboembo-lism’(VTE),among others.Studies comparing the odds ratios(ORs)or risk ratios(RRs)of EOSs with the abovementioned diseases were eligible.Overall,22 studies were included.A high EOS count was associated with acute coronary artery throm-bosis events(OR:1.23,95%CI:1.15-1.32),short-term cerebral infarction and mor-tality(RR:2.87,95%CI:1.49-5.51).The short-term risk of VTE was more common in patients with EOS-related diseases(RR:6.52,95%CI:2.42-17.54).For coronary artery disease,a high EOS count was a protective factor against 6-month to 1-year mortality(RR:0.56,95%CI:0.45-0.69)but was associated with long-term mortal-ity(RR:1.64,95%CI:1.25-2.14).Therefore,we conclude that for coronary artery thrombosis,EOS count is not associated with AMI events in general population.It may be associated with NSTEMI and STEMI in CAD patients,but more studies are needed to confirm this.In addition,EOS count is associated with an increased risk of both short-and long-term mortality but is not predictive of the composite end-points.For cerebral artery thrombosis,EOS count may be associated with cerebral infarction and could lead to an increased risk of poor short-term prognosis.For VTEs,EOS count was a risk factor for some patients,especially those with acute-phase EOS-related diseases.

Intestinal eosinophils:characterization of elusive granulocytes as anti-bacterial and immunomodulatory effector cells in colitis

In a recent study published in Nature,Gurtner and colleagues identify active eosinophils(A-Eos)as eosinophil subset with anti-bacterial and immune regulatory functions during intestinal disease.1 Due to the combination of human singe cell transcip-tomics with pre-clinical experimental studies,the authors suggest eosinophils as promising targets for clinical intervention in inflammatory bowel disease(IBD).Eosinophils are known to exhibit versatile functions at mucosal surfaces.Thus,they can sustain the intestinal epithelial barrier as well as intestinal tissue architecture,communicate with other cell subsets and regulate local immune responses.2 However,despite having been associated with a panoply of different diseases including eosinophilic esophagitis or IBD,3 their role and plasticity in gastrointestinal disorders have not been well characterized.

Number and distribution of eosinophils and lymphocytes in the Japanese pediatric gastrointestinal tract:in search of a definition for"abnormally increased eosinophils"

Background Primary eosinophilic gastrointestinal disorders(EGIDs)constitute chronic allergic inflammation.The number of eosinophils is one of the diagnostic criteria;more than 20 eosinophils per high-power field(HPF)in the gastrointestinal(GI)tract are considered abnormal in Japan.However,the quantity of eosinophils considered normal varies according to anatomical location and geographical region;such values have not been reported in Japanese pediatric patients,nor have the numbers of lymphocytes in the normal pediatric stomach.To establish a reference for defining diagnostic criteria for EGIDs,we evaluated the number of eosinophils in the normal Japanese pediatric GI tract.Methods We examined 131 biopsy cases without significant clinical history,endoscopic abnormality,or histological abnor-mality.Immunohistochemical analysis of CD3 and CD20 was performed.Results The mean eosinophil density was highest in the cecum(49.5±22.4 per HPF).Counts of more than 20 eosinophils per HPF were observed in the duodenum[bulb(20.0±9.6)and second portion(30.0±15.8)],terminal ileum(38.3±22.7),cecum(49.5±22.4),ascending colon(42.3±25.3),transverse colon(29.4±17.0),and descending colon(32.2±17.9).Counts of fewer than 10 eosinophils per HPF were observed in the stomach and rectum;a count of fewer than one eosinophil per HPF was observed in the esophagus.More than 100 CD3-positive T cells per HPF were observed in the stomach.Conclusions The mean numbers of eosinophils in the bowel were greater than 20 per HPF.For Japanese pediatrics,the cur-rent threshold eosinophil count should be revised.

Chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease:Correlations with blood eosinophil level

Objective To observe the correlations of chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)with blood eosinophil(EOS)level.Methods Chest CT data of 162 AECOPD patients with elevated eosinophils were retrospectively analyzed.The patients were divided into low EOS group(n=105)and high EOS group(n=57)according to the absolute counting of blood EOS.The quantitative CT parameters,including the number of whole lung bronchi and the volume of blood vessels,low-attenuation area percentage(LAA%)of whole lung,of left/right lung and each lobe of lung,as well as the luminal diameter(LD),wall thickness(WT),wall area(WA)and WA percentage of total bronchial cross-section(WA%)of grade 3 to 8 bronchi were compared between groups.Spearman correlations were performed to analyze the correlations of quantitative CT parameters with blood EOS level.Results LAA%of the whole lung,of the left/right lung and each lobe of lung,as well as of the upper lobe of right lung LD grade 4,middle lobe of right lung WT grade 5,upper lobe of right lung WA grade 4,middle lobe of right lung WA grade 5 and lower lobe of left lung WA grade 3 in low EOS group were all higher than those in high EOS group(all P<0.05).Except for the upper lobe of right lung LD grade 4,the above quantitative CT indexes being significant different between groups were all weakly and negatively correlated with blood EOS level(r=-0.335 to-0.164,all P<0.05).Conclusion Chest CT quantitative parameters of AECOPD patients were correlated with blood EOS level,among which LAA%,a part of WT and WA were all weakly negatively correlated with blood EOS level.

Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis

BACKGROUND Eosinophilic gastroenteritis(EGE)is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract.Glucocorticoids remain the most common treatment method.However,disease relapse and glucocorticoid dependence remain notable problems.To date,few studies have illuminated the prognosis of EGE and risk factors for disease relapse.AIM To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up.METHODS This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022.Clinical records were collected and analyzed.Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival(RFS).RESULTS EGE showed a median onset age of 38 years and a slight female predominance(56.4%).The main clinical symptoms were abdominal pain(89.1%),diarrhea(61.8%),nausea(52.7%),distension(49.1%)and vomiting(47.3%).Forty-three(78.2%)patients received glucocorticoid treatment,and compared with patients without glucocorticoid treatments,they were more likely to have elevated serum immunoglobin E(IgE)(86.8%vs 50.0%,P=0.022)and descending duodenal involvement(62.8%vs 27.3%,P=0.046)at diagnosis.With a median follow-up of 67 mo,all patients survived,and 56.4%had at least one relapse.Six variables at baseline might have been associated with the overall RFS rate,including age at diagnosis<40 years[hazard ratio(HR)2.0408,95%confidence interval(CI):1.0082–4.1312,P=0.044],body mass index(BMI)>24 kg/m^(2)(HR 0.3922,95%CI:0.1916-0.8027,P=0.014),disease duration from symptom onset to diagnosis>3.5 mo(HR 2.4725,95%CI:1.220-5.0110,P=0.011),vomiting(HR 3.1259,95%CI:1.5246-6.4093,P=0.001),total serum IgE>300 KU/L at diagnosis(HR 0.2773,95%CI:0.1204-0.6384,P=0.022)and glucocorticoid treatment(HR 6.1434,95%CI:2.8446-13.2676,P=0.003).CONCLUSION In patients with EGE,younger onset age,longer disease course,vomiting and glucocorticoid treatment were risk factors for disease relapse,whereas higher BMI and total IgE level at baseline were protective.

Intracellular signaling mechanisms regulating the activation of human eosinophils by the novel Th2 cytokine IL-33:implications for allergic inflammation

The novel interleukin(IL)-1 family cytokine IL-33 has been shown to activate T helper 2(Th2)lymphocytes,mast cells and basophils to produce an array of proinflammatory cytokines,as well as to mediate blood eosinophilia,IgE secretion and hypertrophy of airway epithelium in mice.In the present study,we characterized the activation of human eosinophils by IL-33,and investigated the underlying intracellular signaling mechanisms.IL-33 markedly enhanced eosinophil survival and upregulated cell surface expression of the adhesion molecule intercellular adhesion molecule(ICAM)-1 on eosinophils,but it suppressed that of ICAM-3 and L-selectin.In addition,IL-33 mediates significant release of the proinflammatory cytokine IL-6 and the chemokines CXCL8 and CCL2.We found that IL33-mediated enhancement of survival,induction of adhesion molecules,and release of cytokines and chemokines were differentially regulated by activation of the nuclear factor(NF)-KB,p38 mitogen-activated protein kinase(MAPK)and extracellular signal-regulated kinase(ERK)pathways.Furthermore,we compared the above IL-33 activities with two structurally and functionally related cytokines,IL-1 B and IL-18.IL-1β,but not IL-18,markedly upregulated cell surface expression of ICAM-1.IL-1βand IL-18 also significantly enhanced eosinophil survival,and induced the release of IL-6 and chemokines CXCL8 and CCL2 via the activation of the NF-κB,p38 MAPK and ERK pathways.Synergistic efects on the release of IL-6 were also observed in combined treatment withIL-1B,IL-18 and IL-33.Taken together,our findings provide insight into IL-33-mediated activation of eosinophils via differential intracellular signaling cascades in the immunopathogenesis of allergic inflammation.

CD69 expression on airway eosinophils and airway inflammation in a murine model of asthma

Background Asthma is a chronic airway disease with inflammation characterized by physiological changes （airway hyper-responsiveness, AHR） and pathological changes （inflammatory cells infiltration and mucus production）. Eosinophils play a key role in the allergic inflammation. But the causative relationship between eosinophils and airway inflammation is hard to prove. One of the reasons is lack of activation marker of murine eosinophils. We investigated the expression of CD69 on murine eosinophils in vitro, the relationship between the expression of CD69 on eosinophils from peripheral blood and bronchoalveolar lavage fluid and on airway inflammation in asthmatic mice. Methods Eosinophils from peripheral blood of IL-5 transgenic mice （NJ.1638） were purified. Mice were divided into five groups： wild type mice sensitized and challenged with saline （WS group）, wild type mice sensitized and challenged with ovalbumin （WO group）, IL-5^-/- mice sensitized and challenged with saline and transferred with purified eosinophils （ISE group）, IL-5^-/- mice sensitized and challenged with OVA and transferred with purified eosinophils （IOE group）, IL-5^-/- mice sensitized and challenged with OVA and transferred with purified eosinophils, pretreated with anti CD4 monoclonal antibody （IOE＋antiCD4mAb group）. IL-5^-/- mice were sensitized with OVA at day 0 and day 14, then challenged with OVA aerosol. On days 24, 25, 26 and 27 purified eosinophils were transferred intratracheally to IL-5^-/- mice. On day 28, blood and BALF were collected and CD69 expression on eosinophils measured by flowcytometry. Results Purified eosinophils did not express CD69. But eosinophils cultured with PMA＋MA, IFN- T, IL-5 or GM-CSF expressed CD69 strongly. Eosinophils from blood of WO, WS group did not express CD69 at all. The numbers of eosinophils in BALF of WO group, IOE group, ISE group and IOE＋antiCD4mAb group were significantly higher than in mice of WS group which did not have eosinophils at all. CD69 expression on eosinophils in BALF of IOE and WO groups was strong. Eosinophils in BALF of ISE and IOE＋antiCDmAb groups did not express CD69. The mucus production result was similar to CD69 expression. There were eosinophils infiltration in lung slides of all groups except WS group. Conclusion Activation in airway of eosinophils could directly lead to airway inflammation.

NOD-like receptors mediated activation of eosinophils interacting with bronchial epithelial cells： a link between innate immunity and allergic asthma

Key intracytosolic pattern recognition receptors of innate immunity against bacterial infections are nucleotide-binding oligomerization domain （NOD）-Iike receptors （NLRs）. We elucidated the NOD1 and NOD2-mediated activation of human eosinophils, the principal effector cells for allergic inflammation, upon interacting with human bronchial epithelial BEAS-2B cells in allergic asthma. Eosinophils constitutively expressed NOD1,2 but exhibited nonsignificant responses to release chemokines upon the stimulation by NOD1 ligand 7-D-glutamyl-meso-diaminopimelic acid （iE-DAP） and NOD2 ligand muramyl dipeptide （MDP）. However, iE-DAP and MDP could significantly upregulate cell surface expression of CD18 and intercellular adhesion molecule （ICAM）-I on eosinophils and ICAM-1 on BEAS-2B cells, as well as induce chemokines CCL2 and CXCL8 release in the coculture system （all P〈0.05）. Both eosinophils and BEAS-2B cells were the main source for CXCL8 and CCL2 release in the coculture system upon iE-DAP or MDP stimulation. Direct interaction between eosinophils and BEAS-2B cells is responsible for CCL2 release, and soluble mediators are implicated in CXCL8 release. ERK and NF-KB play regulatory roles for the expression of adhesion molecules and chemokines in coculture. Treatment with NOD1,2 ligand could induce the subepithelial fibrosis and significantly enhance the serum concentration of total IgE, chemokine CCL5 for eosinophils and T helper type 2 （Th2） cells and asthma Th2 cytokine IL-13 in bronchoalveolar lavage fluid of ovalbumin-sensitized allergic asthmatic mice （all P〈0.05）. This study provides further evidence of bacterial infection-mediated activation of NOD1,2 in triggering allergic asthma via the activation of eosinophils interacting with bronchial epithelial cells at inflammatory airway.

NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation

The skin of patients with atopic dermatitis （AD） has a unique predisposition for colonization by Staphylococcus aureus （S. aureus）, which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 （NOD2） and toll-like receptor 2 （TLR2） ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions, Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil-fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway bv which S. aureus contributes to the DathoDhvsiology of AD.

Protein kinase C in proliferation and infiltration of eosinophils in nasal polyp

Objective To explore the significance of protein kinase C (PKC) in proliferation and infiltration of eosinophils in nasal polyps. Methods With in situ hybridization and immunohistochemistry staining methods,PKC,pro-apoptotic,and anti-apoptotic gene (Bax,bcl-2 ) expressions were measured in nasal polyp tissues from 26 patients and inferior turbinate mucosa tissues (ITMTs) from 20 healthy persons. The May-Grünwald-Giemsa (MGG) staining method was used to identify eosinophils. Results In eosinophils,the positive cell expressive rates of Bcl-2 mRNA and its protein were significantly higher in the group with nasal polyps than in the ITMT group ( P <0.01). Although the positive cell expressive rate of Bax mRNA and associated protein were a little higher in the group with nasal polyp tissues than in the ITMT group,the difference was not significant ( P >0.05). There was PKC expression in the eosinophils of 26 cases of nasal polyps,but occasional PKC expression in 7 of 20 ITMT cases. In the two groups,PKC positive cell expression was significantly different,and the expression of PKC and bcl-2 mRNA as well as associated protein in eosinophils of nasal polyps showed a remarkably positive relationship ( r 1=0.0875,r 2=0.0823,P <0.01). Conclusions Increased PKC expression in eosinophils of nasal polyp tissues is closely associated with apoptosis inhibition,and it is presumed that eosinophil apoptosis inhibition in nasal polyp tissues is obtained by activation of the PKC signal transduction pathway.

Animal models of eosinophilic esophagitis,review and perspectives

Eosinophilic oesophagitis(EoE)is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction.Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response,the exact pathogenesis is complex,and the efficacy of existing treatments is unsatisfactory.Therefore,the study of the pathophysiological process of EOE has received increasing attention.Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents.To maximize the use of existing animal models of EOE,it is important to understand the advantages or limitations of each modeling approach.This paper systematically describes the selection of experimental animals,types of allergens,and methods of sensitization and excitation during the preparation of animal models of EoE.It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.

Efficacy of borneol-gypsum in skin regeneration and pain control in toxic epidermal necrolysis:A case report

BACKGROUND Toxic epidermal necrolysis(TEN)is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions.Standard management includes discontinuation of culprit drug and application of immunomodulatory therapy.However,mortality remains high due to complications like septic shock and multiorgan failures.Innovative approaches for skin care are crucial.This report introduces borneol-gypsum,a traditional Chinese drug but a novel dressing serving as an adjuvant of TEN therapy,might significantly improve skin conditions and patient outcomes in TEN.CASE SUMMARY A 38-year-old woman diagnosed with eosinophilic granulomatosis with polyangiitis experienced gangrenous complications and motor nerve involvement.After initial treatment of high-dose corticosteroids and cyclophosphamide,symptom of foot drop improved,absolute eosinophil counts decreased,while limb pain sustained.Duloxetine was added to alleviate her symptom.Subsequently,TEN developed.Additional topical application of borneol-gypsum dressing not only protected the skin lesions from infection but also significantly eased localized pain.This approach demonstrated its merit in TEN management by promoting skin healing and potentially reducing infection risks.CONCLUSION Borneol-gypsum dressing is a promising adjuvant that could significantly improve TEN management,skin regeneration,and patient comfort.

Acute Eosinophilic Pneumonia (AEP) Due to Daptomycin: Is Autoimmunity a Clinico-Pathophysiologic Bridge to AEP?

Daptomycin induced acute eosinophilic pneumonia is a rare and potentially life threatening condition characterized by rapid respiratory failure, pulmonary infiltrates and eosinophilia. Risk factors for acute eosinophilic pneumonia include smoking, environmental irritants or inhalants and certain medications such as Daptomycin [1]. In this review of literature, we aim to explore the potential triggers for developing acute eosinophilic pneumonia in patients exposed to Daptomycin. The exact immune mechanism for daptomycin induced AEP is unknown, however the current proposed mechanism describes a T helper 2 lymphocyte response to inactivated daptomycin in the pulmonary surfactant, which leads to eosinophilia. Disordered T regulatory cell function is seen in patients with certain cancers, allergies and autoimmune conditions. We propose that patients with these underlying risk factors may be at increased risk of developing AEP after becoming exposed to Daptomycin. Understanding potential risk factors is crucial for health care workers as it allows them to identify susceptible populations, explore preventative measures and treat accordingly.