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Ratio of serum eosinophil cationic protein/blood eosinophil counts in children with asthma: comparison between acute exacerbation and clinical remission.

Serum eosinophil (Eo) cationic protein (ECP) concentrations during acute exacerbations in asthma patients are significantly elevated compared with those during clinical remission. We measured the ratio of serum ECP concentration to peripheral blood Eo counts (ECP/Eo ratio), to determine whether the ECP release from Eo differs between the two clinical asthma situations. Forty-six children with asthma underwent spirometric assessment and blood sampling at the times of acute exacerbation and clinical remission. Twenty healthy children also were studied as a control group. The peripheral blood Eo count (468 +/- 262 per microL, mean +/- SD), the serum ECP concentration (41.7 +/- 16.9 micrograms/L), and the ECP/Eo ratio (0.104 +/- 0.049) during acute asthma exacerbations were significantly higher than the respective values during clinical remission (383 +/- 191 per microL, 27.4 +/- 11.5 micrograms/L, 0.084 +/- 0.041, all p < 0.05). The ECP/Eo ratio as well as the serum ECP concentration during acute exacerbations correlated significantly with the degree of airflow obstruction (both, p < 0.01). Both the increased peripheral blood Eo counts and the possible enhanced Eo activation may account for the elevated serum ECP concentration observed during acute exacerbations compared with that during clinical remission. Our results suggest a differential release of ECP by the Eo, depending on the disease status and asthma exacerbation severity.

Acute Disease↗

Eosinophil activation in acute and chronic chagasic myocardial lesions and deposition of toxic eosinophil granule proteins on heart myofibers.

Cardiac lesions in patients with Chagas' disease are infiltrated with various types of inflammatory cells, including eosinophils (EOS). We determined the proportions of resting and activated EOS in 2 types of chagasic myocardial lesions to establish whether their presence correlated with lesion severity. One lesion type was defined by interstitial infiltration associated with degeneration and necrosis of myocardial fibers; the other type presented mild myocarditis but myofibers were preserved. In all cases (1 patient with acute and 5 patients with chronic Chagas' disease), a marked degree of EOS infiltration was seen in the necrotic areas after staining either with Giemsa or immunohistochemically, using antibodies specific for the EOS cationic protein or the major basic protein of the granule. In contrast, a very small number of EOS was present in areas of the very same tissue sections displaying mild myocarditis and preserved myofibers. Of the EOS present in the necrotic areas, 42-78% were in the activated secretory stage as evidenced immunohistochemically after incubation with a monoclonal antibody specific for an epitope of the secretory but not the storage form of the EOS cationic protein. In areas with mild myocarditis this proportion was much smaller, ranging from 9 to 28%. In all cases, both the total level of resting and activated EOS in the necrotic areas correlated well with the overall degree of severity of myocarditis evaluated histopathologically. Deposits of the major basic cationic proteins of the EOS granules were found on myofibers in the necrotic areas from the acute and chronic cases, indicating EOS degranulation.

Acute Disease↗

Isolation of an eosinophil chemotactic lymphokine as a natural mediator for eosinophil chemotaxis from concanavalin A-induced skin reaction sites in guinea-pigs.

An intradermal injection with 20 micrograms concanavalin A (Con A) induce a marked tissue eosinophilia peaking at 24 h after the injection in guinea-pigs. Two different eosinophil chemotactic factors (ECFs) were isolated from the Con A-induced skin reaction sites. A non-dialysable ECF with mol. wt of about 70,000 closely resembled delayed ECF-a, which had been isolated from active cutaneous anaphylactic skin lesions and confirmed to be a product of T lymphocytes by antigenic stimulation, by virtue of the antigenicity, the chromatographic profiles on Sephadex G-100 and on DEAE-Sephadex, affinity to Con A-Sepharose, and other physicochemical properties. The activity of the factor paralleled the intensity of tissue eosinophilia, suggesting that the factor may function for the tissue eosinophilia as a natural mediator. Although another ECF with a low mol. wt (dialysable) was isolated from the same skin lesions, the dialysable factor may not contribute to the tissue eosinophilia because the activity of the factor paralleled the intensity of tissue basophilia but not that of eosinophilia.

Animals↗

Expression and characterization of recombinant human eosinophil-derived neurotoxin and eosinophil-derived neurotoxin-anti-transferrin receptor sFv.

The gene for the human recombinant eosinophil-derived neurotoxin (rEDN) was synthesized and fused to the gene encoding a single chain antibody (sFv) to the human transferrin receptor (EDNsFv). Both rEDN and EDNsFv were expressed as insoluble proteins in inclusion bodies in Escherichia coli BL21(DE3). Following denaturation and renaturation, EDN and EDNsFv were partially purified by chromatography on heparin-Sepharose. Final purification of EDN was achieved by Sephadex G-100, whereas EDNsFv which contained a 6-histidyl residue carboxyl terminus was highly purified using the metal chelate resin, Ni(2+)-nitriloacetic acid. Whereas the recombinant EDN had ribonuclease activity that was similar to the native protein, the fusion protein had enzymatic activity that was 6-13% that of native EDN. The fusion protein was able to bind to the human transferrin receptor. In contrast to rEDN that had no inherent cytotoxicity to human tumor cells, the EDNsFv fusion protein was cytotoxic to human leukemia cells that express the human transferrin receptor with an IC50, 0.2-1 nM. At 1.3 nM EDNsFv, no cytotoxicity was observed on cells that lack the human transferrin receptor. Free antibody to the human transferrin receptor, E6, inhibited the cytotoxicity of the EDNsFv. Human enzymes may be engineered to acquire cytotoxic properties by fusing them to antibodies. Thus, they may be candidates for the construction of immunofusion proteins that may be less immunogenic than immunotoxins containing bacterial- or plant-derived toxin moieties.

3T3 Cells↗

Salbutamol pretreatment does not change eosinophil percentage and eosinophilic cationic protein concentration in hypertonic saline-induced sputum in asthmatic subjects.

BACKGROUND: Sputum induction by inhalation of hypertonic saline (HS) is usually preceded by beta2-agonist pretreatment, to prevent severe bronchoconstriction. OBJECTIVE: To evaluate whether salbutamol pretreatment may influence cell counts and concentrations of soluble mediators in induced sputum. METHODS: We studied 22 patients who randomly underwent HS sputum induction after pretreatment with either 200 microg salbutamol or placebo. Sputum was induced by means of HS inhalation (3, 4, 5% NaCl, 10 min each), measuring FEV1 every 5 min until it fell >/= 20% from baseline. Collected sputum was diluted 1 : 1 with 0.1% DTT, incubated at 37 degrees C for 20 min, and total and differential cell counts were measured. ECP and histamine levels were measured in the supernatant. RESULTS: Sputum volume, percentages of inflammatory cells, squamous cell counts and quality of the slides were not different after the two pretreatments, while sputum total inflammatory cells after salbutamol tended to be higher than after placebo (8.3 [1-41] 10(6) vs 6.3[0.2-40] x10(6); P = 0.09). Eosinophilic cationic protein (ECP) did not significantly change (260 [8-900] microg/L after salbutamol vs 200 [8-800] microg/L, n = 19), while histamine levels tended to be lower after salbutamol (140.9 [39.9-236.5] nm) than after placebo (190.4 [72. 2-322.6] nm, P = 0.09, n = 17). The airway response to HS inhalation was significantly greater after placebo and the duration of the test was significantly different (median: 15 min after placebo and 30 min after salbutamol). Similar results were obtained when patients who differed for more than 15 min in the duration of HS-inhalation in the two tests were selected (n = 11). CONCLUSION: Salbutamol pretreatment reduces the severity of bronchoconstriction induced by HS inhalation without significantly affecting the percentages of inflammatory cells and the levels of soluble mediators in induced sputum.

Adrenergic beta-Agonists↗

Eosinophilic granuloma of the clivus: case report, follow-up of two previously reported cases, and review of the literature on cranial base eosinophilic granuloma.

OBJECTIVE AND IMPORTANCE: To our knowledge, this is the first reported case of the use of stereotactic radiotherapy for an eosinophilic granuloma (EG) of the clivus. We report follow-up information on two previously reported cases and suggest a management plan for this rare lesion. CLINICAL PRESENTATION: We report the case of a 4.5-year-old boy who presented with a complete abducens palsy on the right with an associated head turn. A computed tomographic scan of his head revealed a lytic lesion on that side, and magnetic resonance imaging showed the mass to be of low intensity on T1-weighted images and of high intensity on T2-weighted images with heterogeneous enhancement. INTERVENTION: A transnasal stereotactic biopsy was performed, revealing an EG. The patient was treated with stereotactic radiotherapy, and he became symptom-free with radiographic resolution of his lesion. Reviewing the literature, we found 13 series with 87 cases of EG in the petrous portion of the temporal bone. EG in the cranial base occurring outside of the temporal bone or in the temporal bone and extending intracranially is, however, quite rare, with only nine other cases reported, two of them clival. CONCLUSION: These findings suggest a classification schema in which cranial base EG lesions be grouped with either the more common extracranial petrous temporal bone lesions or the very rare intracranial lesions. Although there are few cases in the literature, treatment results indicate that clival EG, and perhaps all intracranial cranial base EGs, be treated by a biopsy alone, followed by surgery or stereotactic radiotherapy if there is an incomplete resolution of the symptoms or if there is a recurrence.

Child, Preschool↗

Eosinophil-rich CD30+ lymphoproliferative disorder of the oral mucosa. A form of "traumatic eosinophilic granuloma".

We describe 3 patients who had oral mucosal lesions with features of traumatic eosinophilic granuloma (TEG) and containing CD30+ atypical cells. In 1 patient, the oral lesion was followed by skin nodules. All lesions were evaluated histologically, by immunohistochemical analysis, and by polymerase chain reaction (PCR) analysis of the T-cell receptor (TCR) gamma chain gene. All oral lesions were characterized by a dense and deeply infiltrative lymphoproliferation, showing epitheliotropism and massive eosinophilia. They contained atypical large lymphoid cells, which expressed T-cell markers and CD30. PCR analysis showed a monoclonal rearrangement of the TCR gamma chain gene in all lesions and, in 1 patient, the same rearrangement in the oral and cutaneous specimens. The lesions in these patients seem to be the oral counterpart of the spectrum of primary cutaneous CD30+ lymphoproliferative disorders and should be recognized as such to avoid a diagnosis of large T-cell lymphoma and possible consequent overtreatment. However, they represent only a subset among several others within the complex and heterogeneous category of disorders referred to as TEG.

Adult↗

Hyperleukocytosis with marked hypereosinophilia. Morphologic and cytochemical pathologic aspects of eosinophils. Eosinophilic leukaemia?

Excluding the most frequent pathologies that cause hypereosinophilia, we report a case of a patient with hyperleukocytosis and marked hypereosinophilia that showed morphological abnormalities in conjunction with cytochemical pathologic aspects. Physical examination, laboratory results and cytochemical abnormalities induced us, although a normal karyotype, to consider the possibility of eosinophilic leukaemia.

Aged↗

Ascaris and eosinophil. II. Isolation and characterization of eosinophil chemotactic factor and neutrophil chemotactic factor of parasite in Ascaris antigen.

In the previous study, we found an eosinophil chemotactic factor of the parasite (ECF-P) in extracts from the body cavity fluid of the Ascaris species. In this study, the physiochemical characteristics of ECF-P were determined in order to elucidate the relationship between ECF-P and Ascaris antigens. ECF-P was active in both in vivo and in vitro chemotactic assay systems and was found to be heat labile, nondialyzable, and stable to lyophilization. The estimated m.w. was approximately 30,000 daltons. The isoelectric point of ECF-P was 8.5. It was quite different from the Ascaris antigen in the same extract, or various Ascaris allergens that had been reported previously by other researchers. Furthermore, ECF-P did not show any activity in eliciting a guinea pig passive cutaneous anaphylaxis (PCA) reaction. From these experimental results, we concluded that ECF-P is not identical to Ascaris antigens. In addition, we found that the neutrophil chemotactic factor of the parasite (NCF-P), with at least two components, is present in the Ascaris extract, and is also heat labile and resistant to dialysis and lyophilization, but separable from coexistent ECF-P by reason of their different physiochemical properties.

Animals↗

Eosinophilic gastroenteritis or eosinophilic chloroma?

Granulocytic sarcoma of the small intestine preceding or as the presenting feature of acute myelogenous leukemia with chromosome 16 abnormalities has been observed in at least 4 patients. We report the case of a patient initially diagnosed with eosinophilic gastroenteritis, responding to corticosteroid treatment for 21 months and eventually transforming into an acute myelogenous leukemia with eosinophilia (M4Eo variant).

Adrenal Cortex Hormones↗

Colitis and pericarditis in a patient with eosinophilic fasciitis. A contribution to the multisystem nature of eosinophilic fasciitis.

A case of eosinophilic fasciitis (EF), associated with monoclonal gammopathy, thyroglobulin antibodies, pericarditis and colitis, is described. The occurrence of EF in the framework of a multisystem disease is the outstanding feature, contrasting with the absence of visceral involvement or solitary organ involvement in the large majority of cases. The unusual histologic features of the colitis and beneficial effect of cimetidine on EF are discussed.

Aged↗