Cellular Localization of Profibrinolysin (Plasminogen)

A previously unrecognized property of the human eosinophil is described;namely, profibrinolysin localization within the eosinophilic granules of bonemarrow cells. For this demonstration the fluorescent antibody technic wasemployed. Highly specific fluorescent antiprofibrinolysin marked all membersof the eosinophilic series. As maturation proceeded, the profibrinolysin content increased with the greatest intensity of fluorescence seen in the matureeosinophils. These findings are compatible with the view that the bone marrow eosinophil is the site of profibrinolysin synthesis.

Mature eosinophils in peripheral blood smears consistently stained lessintensely. Apparently profibrinolysin is tranported from the marrow and released to the circulation and tissues when needed. These findings may beinterpreted as indicating a role of the eosinophil in clot lysis and in maintaining the fluidity of the blood.

     

Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases

Eosinophilic endomyocardial disease represents a major evolutive risk in chronic eosinophilia-associated disorders. Eosinophil granule proteins appear to be involved in cardiac injury, but the mechanisms leading to eosinophil infiltration and degranulation are not clear. Interleukin-5 (IL-5) has been recently shown to be produced by eosinophils and might play a role in both chemoattraction and degranulation of eosinophils. In four cases of eosinophilic diseases with severe cardiac failure, we evaluated the proportion of eosinophil phenotypes and the serum levels of eosinophil cationic protein (ECP) and soluble IL-2 receptor (sIL-2R), markers of disease activity in the hypereosinophilic syndromes. All four patients showed a markedly increased proportion of hypodense eosinophils with elevated serum ECP and sIL-2R levels. In all four patients, extracellular deposition of eosinophil granule proteins and features of eosinophil activation were observed in cardiac tissues. The synthesis of IL-5 by eosinophils was detected in myocardial sections and blood cells by in situ hybridization and by immunostaining with a monoclonal antibody against human IL-5. Sixty percent to 90% of tissue eosinophils expressed IL-5 mRNA and IL-5 protein. These data suggest that IL-5 can be produced by eosinophils at the sites of myocardial tissue damage and might participate in local eosinophil activation.     

Deposition of autofluorescent eosinophil granules in pathologic bone marrow biopsies

Eosinophil granules are intensely autofluorescent when excited by green light. To determine if eosinophils degranulate in the bone marrows of patients with a variety of diseases, we used green light epifluorescence microscopy to examine deparaffinized and dezenkerized sections of 49 bone marrow core biopsies. In 14 of the biopsies, there was striking extracellular deposition of intensely autofluorescent eosinophil granules in addition to numerous intact eosinophils. Among the 14 specimens with extracellular autofluorescence were seven cases of leukemia, four cases of non-Hodgkin's lymphoma, two cases of myelofibrosis, and one case of pancytopenia with eosinophilia. In the remaining 35 specimens, only intact eosinophils were identifiable. There was no extracellular autofluorescence in three normal marrows, four marrows from AIDS patients, or three biopsies from patients with idiopathic thrombocytopenic purpura (ITP). We conclude that green light epifluorescence microscopy identifies extracellular deposits of eosinophil granules in bone marrow biopsies of some neoplastic disorders and in diseases associated with reticulin fibrosis.     

Activated eosinophils and interleukin 5 expression in early recurrence of Crohn's disease.

Endoscopic recurrences after radical surgery for Crohn's disease are useful for studying the pathogenesis of initial lesions of Crohn's disease. Factors predisposing to recurrence are poorly understood, but it has been shown that eosinophilic infiltration of the neoileum may occur within a few weeks of resection. The aim of this study was to compare, in nine patients having an ileocolectomy, the infiltration of eosinophils and their activation state in normal and diseased areas of the neoileum, three months after surgery. Tissue eosinophils were studied by histochemical methods and electron microscopy. Mucosal expression of interleukin 5 (IL 5), an important eosinophil activating factor was studied using in situ hybridisation. Sixty per cent of patients had endoscopic recurrence at three months. Eosinophil infiltration was more pronounced in diseased than in endoscopically normal areas and was associated with a high expression of IL 5 mRNA. Ultrastructural analysis showed features of eosinophil activation, but no cytotoxic lesions of surrounding inflammatory or epithelial cells. This study suggests that local synthesis of IL 5 associated with eosinophil activation in the tissues could participate in early mucosal damage in Crohn's disease.     

Sputum CD34+IL-5Ralpha+ cells increase after allergen: evidence for in situ eosinophilopoiesis

Eosinophil lineage-committed progenitors increase in the bone marrow of subjects with asthma developing allergen-induced airway hyperresponsiveness and eosinophilia. Also, higher numbers of circulating eosinophil/basophil cfu have been demonstrated 24 hours after allergen inhalation and in bronchial and nasal biopsies of allergic individuals. These cells may undergo in situ eosinophilopoiesis, suggesting that after allergen inhalation, progenitor cells traffic from the bone marrow to the airways, providing an ongoing source of effector cells. To examine this possibility, CD34(+) and CD34(+)IL-5Ralpha(+) cells were measured in induced sputum from allergic subjects with asthma at baseline and at 7 and 24 hours after allergen and diluent inhalation, using flow cytometry. Isolated early responders (n = 9) were contrasted to dual responders (n = 9), who develop allergen-induced sputum and blood eosinophilia and airway hyperresponsiveness, and to normal control subjects. At baseline, there were significantly fewer sputum eosinophils and CD34(+) cells in normal control subjects compared with subjects with asthma. Sputum CD34(+) cells increased at 7 hours after allergen inhalation in both groups of subjects with asthma, which was sustained at 24 hours in the dual responder group only, associated with sustained increases in sputum CD34(+)IL-5Ralpha(+) cells, eosinophils, and interleukin-5. These results indicate that eosinophil progenitors can migrate to the airways and may differentiate toward an eosinophilic phenotype.     

未控制支气管哮喘患者痰嗜酸粒细胞水平与肺功能相关性分析

目的:分析未控制支气管哮喘(哮喘)患者不同水平痰嗜酸粒细胞的临床特点,探讨未控制哮喘患者痰嗜酸粒细胞与肺功能的相关性。方法:纳入2017年8月至2019年9月就诊于内蒙古自治区人民医院呼吸与危重症医学科的未控制哮喘患者167例病例资料进行回顾性研究,根据诱导痰嗜酸粒细胞百分比结果将患者分为2组,以痰嗜酸粒细胞百分比≥2...     

Effects of human mast cell tryptase and eosinophil granule proteins on the kinetics of blood clotting

Hypereosinophilic syndromes are often associated with thrombosis through unclear mechanisms, and mastocytosis has been associated with a variety of bleeding disorders. The present studies were aimed at defining the roles and interactions of eosinophil and mast cell constituents on the kinetics of blood clotting as measured by thromboelastograms. Eosinophil granule proteins and purified eosinophil peroxidase markedly reduced the anticoagulant properties of the mast cell tryptase/heparin complex. Moreover, eosinophil peroxidase by itself functioned as a powerful procoagulant and also inhibited the anticoagulant actions of heparin in a chromogenic assay for antithrombin III/factor Xa activity. The anticoagulant activity of the tryptase/heparin complex was attributable exclusively to the associated heparin and not to the intrinsic enzymatic activity of tryptase. Eosinophil granule proteins also strongly inhibited the enzymatic activity of tryptase in the presence of hydrogen peroxide, thus implicating a critical role for eosinophil peroxidase. We conclude that eosinophil granule proteins and eosinophil peroxidase both function as powerful procoagulants and also inhibit the anticoagulant and enzymatic activities of mast cell tryptase. The present results thus provide a mechanistic rationale for the well-established link between certain eosinophilic inflammatory disorders and hypercoagulant states. They also suggest that eosinophils may play an important role in neutralizing the anticoagulant activity of mast cell tryptase/heparin in various diseases.     

Eosinophil colony formation in semisolid cultures of human bone marrow cells.

A method for in situ staining and scoring of eosinophil colonies and clusters in the whole culture dish has been developed for agar cultures of human marrow cells. Cultures stimulated by human placental conditioned medium were found to develop the same proportion of eosinophil, neutrophil, and monocyte colonies as cultures stimulated by conventional peripheral white cell underlayers. Eosinophil colonies and clusters always contained pure populations of eosinophils, and no mixed colonies of eosinophils with other cells were observed. Eosinophil colony formation was delayed in onset relative to neutrophil or monocyte colony formation, but by day 14 eosinophil colonies comprised 20% of all colonies. Eosinophil colonies were absent in cultures of marrow cells from patients with acute myeloid leukemia in relapse, but eosinophil colonies and clusters were found with higher than normal frequency in cultures from acute leukemic patients in remission. A high frequency of eosinophil colonies and clusters was also observed in cultures from three patients with idiopathic thrombocytopenic purpura. The new staining procedure should permit a wide range of studies on eosinophil precursor populations in the marrows of patients with various diseases.     

The pathogenesis of eosinophilic endomyocardial disease in patients with carcinomas of the lung

Summary Studies were done on a patient with a carcinoma of the lung induced by hypereosinophilia who was thought to be at risk from developing eosinophilic endomyocardial disease to see whether the development of heart disease could be related to abnormalities in the morphology or kinetics of blood eosinophils. The patient was a 61-year-old man who had a partial resection of a squamous cell bronchial carcinoma of anaplastic large cell type which had spread locally. Seven months later, he developed a blood eosinophil count of 33.9 × 10⁹/l. There were only transient responses to treatment with steroids and tumor irradiation, and he died 15 weeks later. Up to 3 × 10⁹/l blood eosinophils were degranulated, correlating with serum levels of eosinophil cationic protein. The blood half-life of¹¹¹indium-labeled eosinophils was prolonged to 53 h, but their distribution was normal. Although an unsuccessful search was made during life for the development of endomyocardial damage, at postmortem the left ventricle had features of eosinophilic endomyocardial disease in the acute necrotic stage. Among 13 other reported patients with carcinoma of the lung and hypereosinophilia, three also had endomyocardial disease or myocardial lesions. These findings confirm the suggestion that the presence in the blood of >1×10⁹/l degranulated eosinophils can be used to predict the development of eosinophilic endomyocardial disease before it becomes apparent clinically, and they also add weight to the hypothesis that blood eosinophil degranulation causes this complication of hypereosinophilic states.     

Rapidly progressive, refractory eosinophilia with a 250,000/microliter eosinophil count

A 31-year-old man had received corticosteroids for 20 months for treatment of a brain tumor, and his blood eosinophil count ranged from 100/microliter to 1,000/microliter. On June 24th, 1998, he was re-admitted because of dyspnea secondary to left massive pleural effusion. Peripheral blood examination revealed an eosinophil count of 48,000/microliter. The eosinophils were hypersegmented, with abnormal distribution of eosinophilic granules and formation of cytoplasmic vacuoles. Blasts and basophils were not increased, hemoglobin was 13.4 g/dl, and the platelet count was 79,000/microliter. Bone marrow was slightly hypercellular with 55% eosinophils and 0.2% blasts. The patient's karyotype was normal, and Wilms' tumor gene was not detected. Serum IgE was normal and serum vitamin B12 and soluble IL-2 receptor were elevated. Serum levels of eosinophilopoietic cytokines, IL-3, IL-5, and GM-CSF, were low. Specimens of pleural fluid contained many eosinophils. Because the eosinophil count increased to 110,000/microliter on July 2nd, hydroxyurea was started without effect. On July 16th, the eosinophil count reached 167,000/microliter, and vincristine was added. The eosinophil count rose to 253,000/microliter the next day, and cytarabine and daunorubicin were administered, but the patient died of septic shock. Although the clinical course suggested eosinophilic leukemia, monoclonal proliferation of eosinophils was not demonstrated. To our knowledge, this is the highest peripheral blood eosinophil count reported in the literature to date.     

Correlation between eosinophil count,its genetic background and body mass index: The Nagahama Study

BackgroundObesity affects the pathogenesis of various chronic diseases, including asthma. Research on correlations between obesity/BMI and eosinophilic inflammation in asthma has yielded contradictory results, which could be partly ascribed to the absence of epidemiological data on the correlations. We aimed to elucidate the correlations between blood eosinophil count, its genetic backgrounds, and BMI in the general population.MethodsThis community-based Nagahama study in Japan enrolled 9789 inhabitants. We conducted self-reporting questionnaires, lung function tests, and blood tests in the baseline and 5-year follow-up studies. A genome-wide association study (GWAS) was performed in 4650 subjects at the baseline and in 4206 of these at the follow-up to determine single-nucleotide polymorphisms for elevated blood eosinophil counts. We assessed the correlations between BMI and eosinophil counts using a multifaceted approach, including the cluster analysis.ResultsEosinophil counts positively correlated with BMI, observed upon the interchange of an explanatory variable, except for subjects with the highest quartile of eosinophils (≥200/μL), in whom BMI negatively correlated with eosinophil counts. GWAS and human leukocyte antigen (HLA) imputation identified rs4713354 variant (MDC1 on chromosome 6p21) for elevated eosinophil counts, independent of BMI and IgE. Rs4713354 was accumulated in a cluster characterized by elevated eosinophil counts (mean, 498 ± 178/μL) but normal BMI.ConclusionsEpidemiologically, there may be a positive association between blood eosinophil counts and BMI in general, but there was a negative correlation in the population with high eosinophil counts. Factors other than BMI, particularly genetic backgrounds, may contribute to elevated eosinophil counts in such populations.     

Eosinophil infiltration and activation at the gastric ulcer margin in rats

BACKGROUND : Recruitment and activation of eosinophils have been studied intensely in asthma and other allergic diseases. Less is known about the infiltration and behaviour of eosinophils during gastric ulcer healing. AIM : To examine the tissue infiltration and activation of eosinophils in the ulcer margin at different time points after ulcer induction (days 1-15). METHODS : Eosinophil peroxidase (EPO) staining and transmission electron microscopy (TEM) were used to observe eosinophil infiltration and activation in rats with acetic-acid-induced ulcer in the oxyntic mucosa. The distribution of macrophages was evaluated by immunocytochemistry using the macrophage-specific antibodies ED1 and ED2. RESULTS : There was a prominent increase in eosinophils around the ulcer margin at day 1 after ulcer induction, which peaked at day 5. TEM revealed characteristic signs of eosinophil activation, including cytolysis and piecemeal degranulation. Eosinophil cytolysis was the major form of activation, seen most frequently at day 5. A few scattered apoptotic eosinophils could also be observed. In normal controls and sham-operated rats, activated eosinophils were detected rarely. The distribution pattern of infiltrated eosinophils closely resembled that of macrophages at the ulcer margin. However, in the central part of the granulation tissue (at day 5) only macrophages could be found. CONCLUSIONS : There is marked infiltration and signs of activation of eosinophils together with macrophages at the margin of newly formed ulcers.     

Classification of eosinophilic gastrointestinal diseases

Diagnosis of eosinophilic gastrointestinal diseases is based on morphological evaluation with regard to localization and density of eosinophil infiltration of the mucosa and/or deeper parts of the oesophagus, stomach, and bowel in biopsy or resection specimens. As with eosinophils in any tissue, in the majority of diseases they are probably a sequel of acute inflammation and do not indicate any specific disease. Eosinophil morphology includes intact cells with bilobated nuclei and eosinophil granules in the cytoplasm and extracellular tissue following activation/degranulation. There is no fixed number of eosinophils that can be used as a cut-off criterion to define disease. Associated histopathological features observed in eosinophilic gastrointestinal disease depend on the site of manifestation and primary disease. Eosinophils are typically increased in allergy-associated colitis in adults and allergic proctocolitis in infants, eosinophilic gastroenteritis and eosinophilic oesophagitis. Their presence can also suggest a drug-induced eosinophilia or the presence of a parasitic infection. In general, eosinophils are increased in inflammatory bowel disease (IBD). They are seen in reflux oesophagitis, coeliac disease, and microscopic and infectious colitis. Eosinophils may be a feature of polyarteriitis nodosa and Churg-Strauss syndrome, and can accompany connective-tissue disease as well as malignant lymphomas and adenocarcinomas of gastrointestinal mucosa.     

In vivo priming of platelet-activating factor-induced eosinophil chemotaxis in allergic asthmatic individuals.

The cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 are important modulators of eosinophilia and eosinophil function. Eosinophil chemotaxis is known to be particularly sensitive for cytokine priming. In the present study, we compared chemotactic responses of eosinophils derived from peripheral blood of allergic asthmatics to responses of eosinophils from peripheral blood of healthy individuals. Eosinophils from allergic asthmatics exhibited a markedly increased sensitivity in their chemotactic response toward platelet-activating factor (PAF) compared with eosinophils from normal donors. In contrast, C5a-induced eosinophil chemotaxis between both groups was similar. This in vivo-primed phenotype could be mimicked in vitro, by preincubating eosinophils from peripheral blood of healthy individuals with picomolar concentrations of either GM-CSF, IL-3, or IL-5. The chemotactic response of eosinophils derived from the circulation of allergic asthmatic patients toward GM-CSF was significantly lower compared with the response of eosinophils of healthy individuals. Our data strongly suggest that release of cytokines may be an important in vivo priming mechanism for eosinophils in the circulation of allergic asthmatic patients. Such an in vivo priming can subsequently result in selective upregulation and downregulation of chemotactic responses toward various chemoattractants release in the lung tissue.     

Hypereosinophilic syndrome human eosinophil degranulation induced by soluble and particulate stimuli

Eosinophil degranulation induced by the calcium ionophore A23187 and opsonized zymosan particles was examined ultrastructurally in peripheral blood cells obtained from patients with the hypereosinophilic syndrome. Unstimulated hypereosinophilic syndrome eosinophils contained altered, vacuolated cytoplasmic granules and large cytoplasmic crystalloid structures not seen in normal cells. By morphometric analysis of transmission electron micrographs, the hypereosinophilic syndrome eosinophils contained a larger percentage of smaller sized cytoplasmic granules than normal cells. The hypereosinophilic syndrome eosinophils, however, were capable of undergoing noncytotoxic degranulation after stimulation with either A23187 or opsonized zymosan. Hypereosinophilic syndrome eosinophil degranulation was characterized by fusion of the perigranular membranes of adjacent cytoplasmic granules and vesiculation of the fused granules. Granule contents were released intracellularly into vacuoles after ionophore stimulation and into phagosomes containing the ingested zymosan particles. Noncytotoxic extracellular release of eosinophil peroxidase (EPO) was also observed after cell stimulation by either A23187 or zymosan. The capacity of hypereosinophilic syndrome eosinophils to degranulate after appropriate stimulation with release of toxic granule constituents such as EPO and other basic proteins may be important in the tissue injury observed in this syndrome.     

Age-related changes in eosinophil function in human subjects

BACKGROUND: Aging results in changes in immune cell function that have been described for T-cells, macrophage, neutrophils, and dendritic cells but not for eosinophils. We sought to define age-related changes in eosinophil function and their potential implications for asthma. METHODS: We recruited human subjects with asthma in two age groups: a younger group (20 to 40 years), and an older group (55 to 80 years). Lung function, induced sputum, and peripheral blood were obtained from each subject. Eosinophils isolated from the peripheral blood were examined for in vitro functional activities including degranulation, superoxide anion production, adhesion, and chemotaxis. RESULTS: Eosinophil degranulation in response to interleukin-5 stimulation was significantly decreased in the older group (p = 0.025). Eosinophil production of superoxide anions in response to phorbol myristate acetate was lower in the older group but did not achieve statistical significance (p = 0.097). Eosinophil adhesion, eosinophil chemotaxis, lung function, and the percentage of sputum eosinophils were similar in the two groups. CONCLUSION: Airway eosinophilia is comparable in younger and older asthma subjects. However, there are age-related changes in peripheral blood eosinophil "effector" functions. Diseases such as asthma, in which eosinophils are thought to play a pathophysiologic role, may exhibit important clinical differences in the elderly due to age-related changes in inflammatory cell function that affect the manifestations of the disease and/or responsiveness to specific classes of medications.     

Human eosinophil hematopoiesis studied in vitro by means of murine eosinophil differentiation factor (IL5): production of functionally active eosinophils from normal human bone marrow

The production of human eosinophils in vitro from normal bone marrow by using murine eosinophil differentiation factor (mEDF/interleukin 5) is described. Eosinophil production was selective and first detectable after 14 days and reached a peak between 21 and 35 days when they were the predominant cell type (41% to 89%). Until day 14, all the eosinophils were typical myelocytes, developing thereafter into metamyelocytes and mature cells. All cell types had characteristic light- and electron-microscopic features, apart from the absence of granules with crystalline cores. The eosinophils produced were readily recovered, and both immature myelocytes and mature cells were functionally active in an antibody-dependent, cell-mediated cytotoxicity assay. mEDF added into the assay enhanced the cytotoxicity but to a lower degree than previously reported for peripheral blood eosinophils, which suggests that they may be partially activated. The possibility that eosinophils could be deactivated was tested by removing mEDF from the culture medium. The eosinophils retained viability and functional activity, however, and showed no increased ability to be activated by mEDF for up to six days after removing the mEDF. The liquid culture of human bone marrow was shown to be an alternative assay for eosinophil differentiation factors to colony formation.     

Eosinophil activation by colony-stimulating factor in man: metabolic effects and analysis by flow cytometry

Substantial increases in the killing capacity of human eosinophils after in vitro incubation with human placental conditioned medium (HPCM), a standard source of colony-stimulating factor (CSF), have recently been described. In this article, the interaction between HPCM and purified human eosinophils is analyzed by flow cytometry and by effects on iodination, superoxide production, and protein synthesis. HPCM increased the intensity of natural eosinophil autofluorescence (aFlu) (460 nm) after the absorption of ultraviolet light (360 nm) in a manner that was both time and dose dependent. Measured in arbitrary units, eosinophil aFlu was 72 +/- 7.3 (arithmetic mean +/- SEM) and 121 +/- 3.2 after 18-hr incubations in the absence or presence of HPCM, respectively. The activity in HPCM responsible for these changes cochromatographed on Ultrogel AcA44 columns with CSF and with the less hydrophobic variant of CSF (CSF-alpha) on phenyl Sepharose. Mouse spleen, but not mouse lung, conditioned medium was also active on human eosinophils in this assay. Both CSF-alpha and mouse spleen conditioned medium also contain eosinophil colony-stimulating activity (CSA), whereas inactive CSFs with no effect on mature eosinophils, CSF-beta, and mouse lung conditioned medium also lack eosinophil CSA. CSF-alpha stimulated superoxide production of resting eosinophils (from 0.03 +/- 0.03 to 0.47 +/- 0.08 nmole cytochrome-c reduced/10(5) eosinophils) and of eosinophils incubated with preopsonized zymosan (from 0.15 +/- 0.06 to 0.73 +/- 0.07). It also stimulated iodination by resting eosinophils (from 0.76 +/- 0.16 to 2.60 +/- 0.72 nmoles l/10(7) eosinophils/hr) and of eosinophils incubated with preopsonized zymosan (from 7.52 +/- 2.08 to 29.8 +/- 1.32). In contrast, CSF-beta was inactive in these assays. CSF-alpha also stimulated, between 2- and 15-fold, the new protein synthesis of eosinophils. Thus, substances that stimulate the differentiation of progenitor cells into eosinophils also interact with peripheral mature eosinophils, and the activation of postmitotic cells may be a physiologic role of CSF-like molecules.     

Pattern of airway inflammation and its determinants in children with acute severe asthma.

The aim of this study was to examine the relationship between sputum cell counts and clinical variables in children with an acute exacerbation of asthma. Sputum was successfully obtained from 37 of 42 children presenting to the Emergency Department with acute asthma, using ultrasonically nebulized normal saline (n = 19) or spontaneous expectoration (n = 18). Sputum portions were selected and dispersed, and total and differential cell counts were performed. Sputum supernatant was assessed for eosinophil cationic protein (ECP), interleukin (IL)-5, and IL-8. The exacerbations were of 3 inflammatory cell patterns: eosinophilic (n = 16 or 43% of total), combined eosinophilic/neutrophilic (E/N; n = 13.3 or 35% of total), or noneosinophilic (n = 8 or 22% of total). IL-5 was highest in eosinophilic exacerbations. Combined E/N exacerbations had increased mast cells (77%) and higher sputum ECP levels than eosinophilic exacerbations: 2,146 ng/mL vs. 666 ng/mL (P = 0.04). The speed of onset of the exacerbation was not related to the inflammatory cell profile. Logistic regression identified maintenance asthma treatment (odds ratio (OR), 5.9; 95% confidence interval (CI), 1.3-26.8) and lung function during the acute episode (OR, 4.0; 95% CI, 1.7-93) as significantly associated with the intensity of sputum eosinophilia. Eosinophils were lowest in children who received maintenance treatment with oral corticosteroids compared to those with no background asthma preventer therapy (P = 0.001). In conclusion, we identified three distinct patterns of airway inflammation in children with acute asthma; they included increased eosinophils, combined eosinophilic-neutrophilic infiltration, and a noneosinophilic pattern. Eosinophil degranulation was greatest with the combined eosinophilic/neutrophilic pattern of airway inflammation. Sputum eosinophils were associated with clinical severity, and background asthma therapy, but not with outcome, nor with speed of onset of exacerbations. These different inflammatory cell profiles imply different etiological agents and may require differing treatment strategies.     

Evaluation of tissue eosinophils in eosinophilic pneumonia]

Transbronchial biopsy specimens from ten patients with eosinophilic pneumonia were analysed to see whether the tissue contained activated eosinophils or secreted eosinophil cationic protein. The specimens showed many infiltrated tissue eosinophils in the intraalveolar spaces, and thickened alveolar septae and perivascular areas. Most of these eosinophils stained clearly with degranulation by immunohistochemical studies with monoclonal antibody EG2 (for the secreted form of eosinophil cationic protein), indicating that they were activated eosinophils. On the other hand, although pleural tissue obtained at bullectomy performed after pneumothorax showed eosinophilic infiltration, EG2-positive cells were few. Activated eosinophils may play an important role in the development of pulmonary lesions of eosinophilic pneumonia.