Blood eosinophil count and eosinophil cationic protein (ECP) concentration are risk factors of cardiovascular diseases. This study tested whether and how eosinophils and ECP contribute to vascular calcification and atherogenesis.
Immunostaining revealed eosinophil accumulation in human and mouse atherosclerotic lesions. Eosinophil deficiency in ΔdblGATA mice slowed atherogenesis with increased lesion smooth muscle cell (SMC) content and reduced calcification. This protection in ΔdblGATA mice was muted when mice received donor eosinophils from wild-type (WT), Il4-/-, and Il13-/- mice or mouse eosinophil-associated-ribonuclease-1 (mEar1), a murine homologue of ECP. Eosinophils or mEar1 but not interleukin (IL) 4 or IL13 increased the calcification of SMC from WT mice but not those from Runt-related transcription factor-2 (Runx2) knockout mice. Immunoblot analyses showed that eosinophils and mEar1 activated Smad-1/5/8 but did not affect Smad-2/3 activation or expression of bone morphogenetic protein receptors (BMPR-1A/1B/2) or transforming growth factor (TGF)-β receptors (TGFBR1/2) in SMC from WT and Runx2 knockout mice. Immunoprecipitation showed that mEar1 formed immune complexes with BMPR-1A/1B but not TGFBR1/2. Immunofluorescence double-staining, ligand binding, and Scatchard plot analysis demonstrated that mEar1 bound to BMPR-1A and BMPR-1B with similar affinity. Likewise, human ECP and eosinophil-derived neurotoxin (EDN) also bound to BMPR-1A/1B on human vascular SMC and promoted SMC osteogenic differentiation. In a cohort of 5864 men from the Danish Cardiovascular Screening trial and its subpopulation of 394 participants, blood eosinophil counts and ECP levels correlated with the calcification scores of different arterial segments from coronary arteries to iliac arteries.
Eosinophils release cationic proteins that can promote SMC calcification and atherogenesis using the BMPR-1A/1B-Smad-1/5/8-Runx2 signalling pathway.

The Mas-related G protein-coupled receptor X2 (MRGPRX2) is a multiligand receptor responding to various exogenous and endogenous stimuli. Being highly expressed on skin mast cells, MRGPRX2 triggers their degranulation and release of proinflammatory mediators, and it promotes multicellular signaling cascades, such as itch induction and transmission in sensory neurons. The expression of MRGPRX2 by skin mast cells and the levels of the MRGPRX2 agonists (eg, substance P, major basic protein, eosinophil peroxidase) are upregulated in the serum and/or skin of patients with inflammatory and pruritic skin diseases, such as chronic spontaneous urticaria or atopic dermatitis. Therefore, MRGPRX2 and its agonists might be potential biomarkers for the progression of cutaneous inflammatory diseases and the response to treatment. In addition, they may represent promising targets for prevention and treatment of signs and symptoms in patients with skin diseases or drug reactions. To assess this possibility, this review explores the role and relevance of MRGPRX2 and its activators in cutaneous inflammatory disorders and chronic pruritus.

The present study aimed to investigate the effects of C‑C chemokine receptor type 3 (CCR3) gene knockout on allergic rhinitis (AR) in mice, as well as the underlying molecular mechanisms. Ovalbumin was administrated to CCR3+/+ and CCR3‑/‑ BALB/c mice to establish an AR model. The mice were divided into four groups: i) Normal control (CG), ii) AR model (AR), iii) CCR3 knockout CG (CCR3‑/‑CG) and iv) AR model with CCR3 knockout (CCR3‑/‑AR). Histological sections of nasal mucosae were examined by hematoxylin and eosin staining, which revealed that CCR3 knockout suppressed the invasion of inflammatory cells and relieved the damage of nasal mucosae. Peripheral blood smear and nasal‑washing smears were evaluated by Wright\'s staining. Eosinophil (EOS) numbers in nasal mucosae, peripheral blood, and nasal washings of the various groups were ranked in the order: AR>CCR3‑/‑AR>CG>CCR3‑/‑. mRNA expression levels of CCR3, EOS peroxidase (EPO), EOS cationic protein (ECP), and major basic protein (MBP) in the peripheral serum and nasal washings were detected by reverse transcription‑polymerase chain reaction. Interferon‑γ (IFN‑γ), interleukin (IL)‑4, IL‑10, and immunoglobulin E (IgE) protein levels in the peripheral serum and nasal washings were investigated by ELISA. CCR3 mRNA expression was not detected in the CCR3‑/‑ and CCR3‑/‑AR groups, whereas expression levels in the AR group were markedly higher compared with expression in the CG group. Compared with the CG‑associated groups (i.e., the CG and CCR3‑/‑CG groups), the levels of EPO, ECP, MBP, IL‑4, and IgE were significantly increased in the AR‑associated groups (that is, R and CCR3‑/‑AR). In addition, the CCR3‑/‑AR group mice produced significantly lower levels of EPO, ECP, MBP, IL‑4 and IgE compared with the AR group, whereas the expression levels of IFN‑γ and IL‑10 were increased. CCR3 gene knockout may alleviate EOS invasion and the inflammatory response in AR model mice by reducing the expression levels of EPO, ECP, MBP, IL‑4, and IgE, and increasing the expression of IL‑10 and IFN‑γ.

Objective: To observe serum levels of periostin, ECP, IgE in the antibiotic enterprise workers, and study the role of periostin, ECP, IgE in the development of allergic inflammation. Methods: 90 cases with asthma or rhinitis were enrolled as disease group, another 117 workers exposed to 7-ACA、6-APA dust without suffering from allergic illness, are chosen as group of dust exposed, and 192 healthy workers who didn\'t contact dust were chosen as control group. Questionnaires were used to learn their basic information.Lung function was determined with a portable spirometer.The expression levels of periostin、ECP and IgE in serum were measured by enzyme-linked immuno sorbent assay. Results: The exposure group and disease group had significantly lower forced vital capacity (FVC) , forced expiratory volume in 1 second (FEV(l.0)) , and FEV(l.0)/FVC ratio than the control group (P<0.05) . The disease group had significantly higher eosinophil than the control group (P<0.05) . Compared with the control group, the exposure group, the disease group, asthma subgroup, rhinitis subgroup of serum periostin and IgE increased, the differences are statistically significant (P<0.05) . Serum levels of ECP in the workers of asthma subgroup were significantly higher than that in control group (P<0.05) . Serum expression levels of periostin were positively correlated with IgE, ECP in workers (P<0.001) , serum levels of periostin were negatively correlated with FEV(1.0) in workers (P<0.05) . Multiple logistics regression analysis found that exposure to 7-ACA or 6-APA (OR=3.09, 95%CI: 1.83-5.21) , age>47years (OR=2.53, 95%CI: 1.22-5.26) , higher ECP (OR=1.04, 95%CI: 1.01-1.06) were risk factors for increased serum periostin level. Conclusion: Occupational exposure to 7-ACA or 6-APA can result in higher serum periostin level, exposure to 7-ACA or 6-APA, age>47 years, higher ECP are risk factors for increased serum periostin level.
目的： 观察β-内酰胺类抗生素接触工人血清骨膜蛋白（periostin）、嗜酸粒细胞阳离子蛋白（ECP）、免疫球蛋白E（IgE）水平，探讨其在过敏性炎症发生发展中的作用。 方法： 选取90名接触7-氨基头孢烷酸（7-ACA）、6-氨基青霉烷酸（6-APA）粉尘哮喘或过敏性鼻炎患者为病例组（哮喘亚组32人，鼻炎亚组58人），选取117名接触7-ACA、6-APA粉尘无哮喘或鼻炎等过敏性疾病工人为接触组，选择192名不接触粉尘体检健康者作为对照组。通过问卷调查基本情况，便携式肺功能仪测定肺功能，ELISA法测定血清骨膜蛋白、ECP和IgE水平。 结果： 接触组和病例组工人用力肺活量（FVC）、第1秒用力呼气容积（FEV(1.0)）及FEV(1.0)/FVC均低于对照组，差异有统计学意义（P<0.05）。病例组嗜酸粒细胞计数明显高于对照组，差异有统计学意义（P<0.05）。接触组、病例组、哮喘亚组、鼻炎亚组血清骨膜蛋白、IgE水平均高于对照组，哮喘亚组血清ECP水平高于对照组，差异有统计学意义（P<0.05）。血清骨膜蛋白与IgE、ECP均呈正相关（P<0.01），血清骨膜蛋白与FEV(1.0)呈负相关（P<0.05）。多元logistic回归分析发现，接触7-ACA或6-APA（OR=3.09，95%CI：1.83~5.21）、年龄>47岁（OR=2.53，95%CI：1.22~5.26）、ECP增高（OR=1.04，95%CI：1.01~1.06）为血清骨膜蛋白升高的危险因素。 结论： 职业接触7-ACA、6-APA可导致血清骨膜蛋白表达水平升高，接触7-ACA或6-APA、年龄>47岁、ECP增高可作为骨膜蛋白升高的危险因素。.

BACKGROUND: Colonoscopy can assess disease activity and severity of ulcerative colitis (UC) accurately, but it is invasive and costly. Role of noninvasive biomarkers of intestinal inflammation in evaluation of patients with UC is not well understood. In this study, we assessed fecal eosinophil cationic protein (FECP), fecal myeloperoxidase (FMPO), and fecal calprotectin (FC) as surrogate markers of disease activity and severity in patients with UC, and then evaluated effect of the combination of these markers.
METHODS: Sixty-three UC patients and 59 cases of age-matched controls were investigated. All patients underwent clinical, endoscopic, and histological assessment for disease activity and severity. Fecal samples were analyzed for FECP, FC, and FMPO.
RESULTS: All three fecal biomarkers were elevated in patients compared with controls (P = 0.000). Significant differences were found between inactive UC and controls (P = 0.000). Cases with severe UC had significantly higher FECP levels than those with mild UC (p < 0.05), but there were no significant differences in FC and FMPO levels among disease severity groups. All three biomarkers showed positive correlation with Ulcerative Colitis Activity Index (UCAI). The areas under the ROC curve of FECP, FC, and FMPO were 0.939, 0.783, and 0.785, respectively. Sensitivity and specificity of fecal biomarkers in assessing disease activity were FECP-88.46%, 89.47%; FC-80.77%, 68.42%; and FMPO-84.62%, 63.16%.
CONCLUSIONS: All three fecal biomarkers could be used as surrogate markers for assessing disease activity of UC, and FECP provided superior discrimination than FMPO and FC. Moreover, FECP could distinguish between mild disease and severe disease group.

Historically, eosinophils have been considered as end-stage cells involved in host protection against parasitic infection and in the mechanisms of hypersensitivity. However, later studies have shown that this multifunctional cell is also capable of producing immunoregulatory cytokines and soluble mediators and is involved in tissue homeostasis and modulation of innate and adaptive immune responses. In this review, we summarize the biology of eosinophils, including the function and molecular mechanisms of their granule proteins, cell surface markers, mediators, and pathways, and present comprehensive reviews of research updates on the genetics and epigenetics of eosinophils. We describe recent advances in the development of epigenetics of eosinophil-related diseases, especially in asthma. Likewise, recent studies have provided us with a more complete appreciation of how eosinophils contribute to the pathogenesis of various diseases, including hypereosinophilic syndrome (HES). Over the past decades, the definition and criteria of HES have been evolving with the progress of our understanding of the disease and some aspects of this disease still remain controversial. We also review recent updates on the genetic and molecular mechanisms of HES, which have spurred dramatic developments in the clinical strategies of diagnosis and treatment for this heterogeneous group of diseases. The conclusion from this review is that the biology of eosinophils provides significant insights as to their roles in health and disease and, furthermore, demonstrates that a better understanding of eosinophil will accelerate the development of new therapeutic strategies for patients.

OBJECTIVE: To observe the clinical manifestations of allergic rhinitis mice and the expression changes of the eosinophils CCR3 and the granule protein mRNA in the bone marrow, peripheral blood and nasal lavage fluid.
METHODS: Twenty-four BALB/c mice were randomly divided into the control group, PBS therapy group, siRNA therapy group and the CCR3 siRNA therapy group (n=6). Allergic rhinitis model were sensitized and stimulated by ovalbunfin, and CCR3 siRNA therapy group were administered with CCR3 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 siRNA 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 mRNA, MBP, ECP and EPO expression in bone marrow, peripheral blood and nasal lavage fluid of the CCR3 siRNA therapy group was lower than the PBS therapy group and siRNA 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.

OBJECTIVE: To evaluate the treatment responses of asthmatics with and without sputum eosinophilia to inhaled glucocorticoids, and therefore to verify whether low sputum eosinophils predict poor response to treatment with inhaled glucocorticoids.
METHODS: Forty-two symptomatic asthmatic patients, who had not received glucocorticoid therapy in the 3 months preceding the study, were examined before and 1 month and 3 months after treatment with inhaled glucocorticoids. At each visit, all patients underwent spirometry, symptom scoring and sputum induction. The level of eosinophil cationic protein (ECP) in the sputum supernatants was measured by radioimmunoassay. The patients were divided into 2 groups according to sputum eosinophil (EOS) percentages, an EOS group (EOS > 3%) and a non-EOS group (EOS < 3%). The response to inhaled glucocorticoid therapy (as measured by symptom scores and FEV(1)% pred) and the changes of sputum measurements were compared between the 2 groups.
RESULTS: In the EOS group, the baseline EOS [0.080 (0.063 - 0.178)] and ECP level [(324 +/- 149) microg/L] were significantly higher than those of the non-EOS group [0.017 (0.006 - 0.021) and (152 +/- 68) microg/L, respectively, t = 4.40, 3.33, both, all P < 0.01]. Baseline FEV(1), FEV(1)% pred and symptom scores were not different between the 2 groups [EOS group: (1.98 +/- 0.67) L, (65 +/- 20)%, 7.0 (5.0 - 10.0), non-EOS group: (2.07 +/- 1.05) L, (66 +/- 27)%, 5.0 (2.0 - 9.0), t = -0.62, -0.09, 1.32, respectively, all P > 0.05]. After 1 month and 3 months inhaled glucocorticoid therapy, the sputum EOS, ECP, the symptom score, FEV(1) and FEV(1)% pred were [0.019 (0.010 - 0.060), [0.036 (0.006 - 0.070); (173 +/- 153) microg/L, (173 +/- 122) microg/L; 3.0 (1.0 - 6.0), 3.0 (1.0 - 5.0); (2.42 +/- 0.64) L, (2.43 +/- 0.76) L; (77 +/- 13)%, (77 +/- 18)%; respectively in the EOS group, which were significantly different as compared to baseline values (F = 6.73, 6.71, 5.93, 7.38, 5.78, respectively, all P < 0.05). But in the non-EOS group, the sputum EOS, ECP, the symptom score, FEV(1) and FEV(1)% pred were 0.013 (0.000 - 0.025), 0.012 (0.004 - 0.031), (111 +/- 50) microg/L, (117 +/- 50) microg/L; 3.0 (0.0 - 6.0), 3.0 (1.0 - 7.3), (2.22 +/- 0.86) L, (2.21 +/- 0.24) L, (71 +/- 20)%, (65 +/- 21)%; respectively at 1 and 3 months, which showed that the sputum EOS, FEV(1) and FEV(1)% pred did not change (F = 1.98, 0.80, 1.37, respectively, all P > 0.05), but the ECP level and the symptom score improved (F = 3.78, 3.59, respectively, both P < 0.05). Multiple stepwise regression showed that baseline FEV(1), severity degree and sputum EOS correlated significantly with changes in FEV(1) after treatment. Among the baseline indexes examined, sputum EOS had the highest negative predictive value (89.5%) for the response to treatment.
CONCLUSIONS: In asthmatics with low sputum EOS, inhaled glucocorticoid therapy for 3 months failed to improve pulmonary function. The result confirmed that low sputum EOS was the best predictor for poor glucocorticoid effect in asthma.

Conclusions. Infiltration and activation of eosinophils is a characteristic of nasal polyposis. Allergic reaction is a risk factor for the accumulation of eosinophils in this disease. T-cell-derived interleukin 5 (IL-5) and autosecretion of IL-5 from activated eosinophils may be causative reasons for the extension and persistence of eosinophil inflammation. Objectives. To investigate whether eosinophils were accumulated and activated in nasal polyposis, and the roles of IL-5, eotaxin, and T cells in this process. Materials and methods. A retrospective study was conducted on 17 tissue samples from patients with nasal polyposis with allergy and 26 cases of non-allergic polyposis. Immunohistochemical staining by specific antibodies was carried out using the alkaline phosphatase anti-alkaline phosphatase method and the avidin-biotin complex technique.Results. The number of EG1-positive cells (pan eosinophil marker) was similar to the number of EG2-positive cells (activated eosinophil marker) in all tissue samples, although EG1- and EG2-positive cells were richer in allergic patients than those in non-allergic patients. Both EG1- and EG2-positive cells were correlated with CD3-positive cells (pan T cell marker) and IL-5-producing cells in allergic or non-allergic polyposis. A large proportion of IL-5 producing cells were eosinophils. Eotaxin protein was detected in all tissue samples and dominantly located in epithelial cells. Eotaxin expression between allergic and non-allergic subjects was not significantly different.

OBJECTIVE: To study the relationship between otitis media of effusion (OME) and allergy by investigating eosinophil cationic protein in middle ear effusion ( MECP), middle ear effusion IgE (MIgE) and serum eosinophil cationic protein (SECP).
METHODS: The specimens drawn from 31 patients of OME were tested with Uni-CAP-100 allergic antigen testing system for the MECP, IgE and SECP. The results then were analyzed by statistical methods.
RESULTS: MECP were found in all the effusion specimens of 31 patients, the average concentration of which was 56.88 microg/L. The MECP concentration level in nine specimens (28.1%) was significantly elevated. The average concentration of MIgE was 27.2 ku/L. The MIgE concentration level in three specimens (9.7%) was remarkably increased. There was a positive correlation between the MECP level and the MIgE level( P <0.05). The average concentration of SECP was 5.6 microg/L.
CONCLUSIONS: ECP exists in the middle ear effusion of OME. OME is an allergic inflammatory process more localized in middle ear itself in some patients. There may be a complicated allergic mechanism in OME.