Serum Eosinophil Cationic Protein Concentrations Research Articles

Elevated Serum Eosinophil Cationic Protein Levels in Cystic Fibrosis, Pediatric Asthma, and Bronchiolitis

Serum levels of eosinophil cationic protein (ECP) may correlate with activity in certain disease states, suggesting that eosinophils and their toxic granular products are involved in the pathogenesis of the disease. The aim of this study was to measure the serum concentration of ECP in patients with cystic fibrosis (CF), pediatric asthma, and viral bronchiolitis. The absolute number of blood eosinophils and IgE levels were determined simultaneously. Serum ECP levels were the highest in CF patients (median, 3101 μg/L, ± 463, N = 18), followed by those with asthma (median, 1113 μg/L, ± 795, N = 10) and those with viral bronchiolitis (median, 1281 μg/L, ± 274, N = 9). Control patients with no infection or lung disease all had ECP levels between 2 and 58 μg/L (median, 3.7 ± 14.7 μg/L, N = 10). The CF patients studied had a significantly higher level of ECP when compared to pediatric asthma and viral bronchiolitis patients (p = 0.008). There was no correlation between the IgE level or absolute eosinophil count and the ECP level. Among the CF patients studied, the forced expiratory volume in 1 second (FEV1) and ECP level did show a significant inverse correlation, (p < 0.01, probability). The finding of elevated ECP levels in CF patients indicates the presence of eosinophil activation in these patients. The correlation between ECP and airflow obstruction suggests a role for activated eosinophils in disease pathogenesis.

Clinical value of monitoring eosinophil activity in asthma.

To evaluate the use of eosinophil cationic protein (ECP) in monitoring disease activity in childhood asthma, serum ECP in 175 asthmatic children was assessed. Forty five patients with cystic fibrosis, 23 with lower respiratory tract infections (LRTI), and 87 healthy children were used as controls. Serum ECP concentrations (34.3 micrograms/l v 9.8 micrograms/l) were significantly higher in children with bronchial asthma than in healthy control subjects. In symptomatic patients with asthma serum ECP concentrations were increased compared with those from asymptomatic patients (40.2 micrograms/l v 14.4 micrograms/l), irrespective of treatment modalities (that is steroids, beta 2 agonists, or sodium cromoglycate). Moreover, atopy and infection appeared to be factors enhancing eosinophil activity in bronchial asthma as measured by serum ECP (58.4 micrograms/l v 36.8 micrograms/l and 68.8 micrograms/l v 42.2 micrograms/l, respectively). In a longitudinal trial, antiasthmatic treatment modalities (that is steroids) reduced serum ECP within four weeks (42.2 micrograms/l v 19.0 micrograms/l). In conclusion, the data indicate that (1) eosinophils also play a central part in childhood asthma; (2) serum concentrations of ECP in children with bronchial asthma are related to the disease severity and may thus be used for monitoring inflammation in childhood asthma; (3) eosinophil activity appears to be enhanced by atopy and infection; and (4) longitudinal measurements of serum ECP concentrations may be useful for optimising anti-inflammatory treatment in children with bronchial asthma.

Eosinophil cationic protein(ECP) and eosinophil protein X (EXP) concentrations in serum and bronchial lavage fluid in asthma. effect of prednisolone treatment.

Eosinophil granule proteins may contribute to bronchial hyperresponsiveness in asthma. To measure eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in serum and bronchial lavage fluid from 20 asthmatics and 16 control subjects. To assess the effect on these eosinophil proteins of corticosteroid treatment of asthma. To determine whether serum ECP and EPX measured weekly in a longitudinal study for 10 weeks reflected changes in lung function. Eosinophil granule proteins were measured by radioimmunoassay of bronchial wash (BW), bronchoalveolar lavage (BAL) and serum. Eosinophils were elevated in BAL (P < 0.01), BW (P < 0.01) and blood (P < 0.01) from asthmatics compared with control subjects. Eosinophils cationic protein concentration was significantly elevated in BAL (P < 0.05) and BW from asthmatics (P < 0.01) and EPX was increased in BAL (P < 0.05) and BW (P < 0.01). These changes were also reflected in elevated serum ECP (P < 0.01) and EPX (P < 0.01) concentrations in asthmatic subjects. There was no significant difference between subjects receiving prednisolone and the placebo group, but there was a fall in ECP in BW (P < 0.05) and serum (P < 0.01) and in EPX in BW (P < 0.01) and serum (P < 0.01) within the group receiving prednisolone. In the longitudinal study there was only a significant difference between ECP values associated with highest and lowest peak expiratory flow rate (PEFR) (P < 0.05). These data confirm a role for eosinophil activation in the airway in asthma pathogenesis, and add some support to the hypothesis that corticosteroids may inhibit eosinophil activation in asthma.

Asthmatic symptoms and indoor levels of micro‐organisms and house dust mites

As a part of a worldwide investigation on the prevalence of respiratory symptoms, we have performed a study on the relationship between the indoor environment and asthma-like symptoms in the population of a central Swedish municipality. The study comprised 88 individuals, aged 20-45 years who underwent a structured interview, spirometry, a methacholine provocation test, skin-prick tests and blood samples for measurements of serum concentrations of eosinophil cationic protein (S-ECP), blood eosinophil count and total immunoglobulin E (S-IgE). In the homes, the room temperature, air humidity, respirable dust, house dust mites (HDM) and airborne micro-organisms were measured. The relative humidity in all the homes was found to be above 33%. HDM were found in 13% of homes. In the homes of the 47 subjects with asthma related symptoms, significantly higher total levels of bacteria and mould (P < 0.05) and a higher proportion of detected HDM (OR = 5.3) was found than in subjects with no asthma related symptoms, after adjustment for age, sex, smoking, indoor temperature and air humidity. HDM were found to be an independent risk factor for asthma related symptoms (OR = 7.9) and nocturnal breathlessness (OR = 6.2) (P < 0.05), while the total level of bacteria was a risk factor for asthma related symptoms and wheezing (P < 0.05). We conclude that although HDM is relatively infrequently found in the homes of central-Sweden, the presence of HDM is related to asthmatic symptoms. A relation between levels of airborne bacteria and asthma related symptoms was also found.

Serum eosinophilic cationic protein and lactoferrin related to smoking history and lung function

Some smokers have an accelerated loss of lung function, possibly due to a chronic bronchial inflammation in which granulocytes are involved. Eosinophil cationic protein (ECP) and lactoferrin (LF) are granule proteins in the eosinophil and neutrophil granulocyte, respectively. We wanted to investigate the relationship of serum (s) ECP and LF concentrations to smoking history and lung function alteration. This partly cross-sectional and partly prospective study included 98 nonatopic smokers and 31 lifetime nonsmokers. As participants in a smoking cessation programme, 50 of the 98 smokers ceased smoking for > or = 1 year. Smoking history, lung function and blood samples were obtained at the start of the study, and smokers and ex-smokers also gave blood samples 3, 6 and 12 months later. s-ECP and s-LF were elevated in smokers compared to people who had never smoked. s-ECP was linearly associated with daily cigarette consumption and forced expiratory volume in one second (FEV1) residuals. In a multiple linear regression analysis, low s-ECP and high s-LF were associated with decreased FEV1 residuals. s-ECP and s-LF together accounted for 10.2% of the variation in FEV1 residuals. After smoking cessation, s-ECP and s-LF decreased within 6 months. s-ECP and s-LF are raised in smokers, and may serve as indicators of granulocyte activation. We speculate that they might contribute to prediction of accelerated lung function loss in smokers, but this question needs further investigation in a prospective study.

Eosinophil cationic protein in the sera of patients with Mycoplasma pneumonia.

In 1985 we reported that eosinophilia was found in many children with Mycoplasma pneumonia. We measured the serum concentrations of eosinophil cationic protein (ECP) produced by eosinophils in 25 children with Mycoplasma pneumonia, 25 with asthma and 11 with no disease (normal controls). The mean concentrations (+/- SD) of serum ECP in children with Mycoplasma pneumonia, with asthma and the normal controls were 18.7 +/- 12.6, 23.7 +/- 12.2 and 6.5 +/- 1.4 micrograms/ml, respectively. When compared with those of normal controls, these higher serum concentrations of ECP in children with Mycoplasma pneumonia and asthma were statistically significant (P < 0.001). The data were directly correlated with the presence of eosinophilia (r = 0.349). There was no relationship between the amount of ECP and the age of children with Mycoplasma pneumonia. These results suggest that ECP may work as a factor causing a persistent cough similar to asthma in children with Mycoplasma pneumonia.

Effect of clotting temperature and eosinophil concentration on the eosinophil cationic protein concentration in serum.

Earlier investigations have indicated the need for detailed instructions about the incubation conditions of blood samples before establishment of eosinophil cationic protein concentration in serum. Therefore, the effect of different clotting temperatures and eosinophil concentrations on the serum eosinophil cationic protein concentration was quantified in 40 subjects. Our results show that serum eosinophil cationic protein concentrations strongly depend on the clotting temperature. Blood samples clotted for 1 h at 37 degrees C had 5-10 times higher serum eosinophil cationic protein concentrations than blood samples of the same subject clotted for 1 h at 0 degrees C. Higher eosinophil counts resulted also in increased serum eosinophil cationic protein concentrations.

Markers for eosinophils and T-lymphocytes as predictors of late asthmatic response.

Bronchial allergen challenge was performed on 12 allergic asthmatics during a stable phase of their disease. After resolution of the immediate bronchial response, fractional lung lavage was performed twice, two and 24 h post-challenge. The recovery of eosinophils, eosinophil cationic protein (ECP), eosinophil chemotactic activity (ECA) and immunohistochemical staining of the phenotypically distinct population stainable by the monoclonal antibody CD45RO, agreed to indicate T-memory cells, were assessed in the two lavages. Serial measurements of lung function, and serum concentration of ECP were also done. We found that although the recoveries in bronchial washes of eosinophil cells and ECP tended to increase during the trial, none of these variables predicted the emergence of late phase bronchial response (LPR). Instead, the proportion in the 2-h lavages, of memory-cells or ECA predicted the LPR. These two variables were inversely correlated to each other in the first lavage, suggesting the T-cells to be potential major sources of ECA. The fact that T-cells and ECA, but not markers for eosinophil activation in lavage, predicted the LPR, may suggest T-cell activation to precede the activation of the eosinophils within the lung after a bronchial allergen challenge. There was a close correlation between LPR and serum concentration of ECP obtained at the end of the trial, 24 h post-challenge, suggesting either a delayed or a continuous activation of circulating eosinophils after bronchial allergen challenge.

Degranulation of eosinophils from pollen-atopic patients with asthma is increased during pollen season

The secretion of granule proteins from eosinophils and neutrophils was studied in isolated cells, obtained from 11 pollen-atopic patients with asthma, twice during and twice outside pollen season. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase (MPO) were measured by means of specific radioimmunoassay (RIA). Eosinophils from the pollen-atopic patients obtained during pollen season released significantly more (p less than 0.02) ECP and EPX than cells from the same patients obtained before pollen season. The released amount of ECP and EPX was correlated (r = 0.54; p less than 0.003) to the total pollen count. The release of MPO from neutrophils was only raised (p less than 0.01) at the end of the pollen season. Serum concentrations of ECP and EPX and blood eosinophil counts were significantly raised (p less than 0.002, p less than 0.001, and p less than 0.009, respectively) before pollen season and increased further at the end of the pollen season. There were no changes in lung function during pollen season and consequently no discernible relationships to eosinophil and neutrophil degranulation. We conclude that eosinophils and, to some extent, neutrophils from birch pollen-atopic subjects have an increased propensity to secrete their granule proteins during a pollen season. We suggest that these cells have been primed as a consequence of allergen exposure.

Secretion of granule proteins from eosinophils and neutrophils is increased in asthma

The activity of eosinophil and neutrophil granulocytes with respect to secretion of granule proteins was studied in 30 patients with asthma and with varying severity of their disease. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase was measured by means of specific radioimmunoassays. Eosinophils from patients with asthma released significantly more (p < 0.001) ECP and EPX after 20 minutes of incubation than cells from control subjects without asthma. The release of myeloperoxidase from neutrophils was also somewhat higher (p < 0.03). The serum concentrations of ECP and EPX were also significantly increased (p < 0.001) in the group with asthma. No significant relationships were found between clinical variables and the secretory activity of either eosinophils or neutrophils. We conclude that eosinophils and, to some extent, neutrophils from subjects with asthma have an increased propensity to release their granule proteins, which we suggest is a consequence of priming of these cells.

鼻アレルギーにおける鼻汁中，血清中のｅｏｓｉｎｏｐｈｉｌ ｃａｔｉｏｎｉｃ ｐｒｏｔｅｉｎ（ＥＣＰ）ならびにａｒｙｌｓｕｌｆａｔａｓｅ Ｂに関する研究

Recently four tissue toxic proteins namely major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) were found in eosinophilic leucocytes. Although the characteristics of these proteins concerning tissue damage in the local site of type I allergic reaction have been investigated mainly in lower respiratory tract, the actual clinico-pathological roles of these proteins in nasal allergy are not clarified. Contrary, eosinophils also have histaminase, arylsulfatase, phospholipase D, which are considered to act on a negative feedback mechanism in allergic reaction through inactivation of chemical mediators. Therefore, estimation of ECP and simultaneously arylsulfatase B in nasal secretion and the sera from patients with nasal allergy may clarify the dynamics of clinico-pathological state, especially in the late phase of allergic reaction in each patients. ECP concentrations in the nasal secretions from 22 patients and in the sera from 12 patients with nasal allergy were measured by RIA method. The activities of arylsulfatase B in the nasal secretions and the sera were also estimated in the same specimens as ECP by measuring its hydrolytic activity using p-nitro cathecol sulfate as a substrate. The results obtained were as follows; 1) There was a significant correlation between ECP concentrations in the nasal secretions and the severities of clinical symptoms, especially the degree of nasal obstruction. ECP concentrations also significantly correlated to the score of eosinophilic leucocytes in the nasal smears. 2) The serum ECP concentrations significantly correlated to the number of eosinophilic leucocytes in the peripheral blood, and also showed slight tendency of correlation to the severity of clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated circulating levels of eosinophil cationic protein in uremia as signs of abnormal eosinophil homeostasis.

Circulating levels of eosinophil cationic protein (ECP), an eosinophil-specific granule protein, and peripheral eosinophils were determined in 56 patients with uremia. The patients were on a chronic hemodialysis or CAPD program or treated with diet only. They had normal counts of peripheral eosinophils but on average a threefold increase of the serum ECP concentrations compared with healthy subjects. The intracellular content of ECP in eosinophils isolated from 6 patients on maintenance hemodialysis was normal. The management or duration of the uremic condition did not influence the circulating ECP levels or eosinophil counts. Neither was any relation found between total IgE levels and peripheral eosinophils or serum ECP. The present results are compatible with an accelerated turnover of peripheral eosinophils in uremia. Such a proposed abnormal eosinophil homeostasis should demand an accelerated marrow eosinophil production, thereby explaining the previously reported marrow eosinophilia in azotemic patients.