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PubMed1991

Concurrent eosinophilic fasciitis and cutaneous T-cell lymphoma. Eosinophilic fasciitis as a paraneoplastic syndrome of T-cell malignant neoplasms?

Eosinophilic fasciitis has been reported to precede hematologic malignant neoplasms such as myelomonocytic leukemia, lymphocytic leukemia, and Hodgkin's lymphoma. In this case study, eosinophilic fasciitis occurred concurrently with cutaneous T-cell lymphoma (mycosis fungoides). The clinical diagnosis of eosinophilic fasciitis was based on painful sclerodermatous lesions on the extremities and trunk without acrosclerosis. There was histologic confirmation with edema and lymphocytic inflammation in the superficial muscular fascia and dermis. Deposition of immune reactants was found in the fascia and dermis. In addition, peripheral eosinophilia and circulating immune complexes were detected. The diagnosis of cutaneous T-cell lymphoma (mycosis fungoides) was based on extensive erythematous cutaneous plaques, dermal and epidermal lymphocytic atypia, loss of pan-T-cell immunologic markers, and a cutaneous lesional T-cell receptor beta-chain rearrangement by Southern blot analysis. Eosinophilic fasciitis may occur as a paraneoplastic syndrome associated with hematologic malignant neoplasms, including mycosis fungoides. Cytokines or lymphokines released by activated immunocytes, either malignant leukocytes or normal leukocytes reacting to malignant cells, may be responsible for the eosinophilia and sclerosis seen in these associated hematologic malignant neoplasms.

Aged↗

PubMed1997

[A clinical study of 5 cases of acute eosinophilic pneumonia--the relationship between beginning to smoke and acute eosinophilic pneumonia].

We encountered 5 cases of acute eosinophilic pneumonia. All cases were young men who had recently begun smoking, and they showed an acute onset hypoxemia, diffuse shadows on chest X-ray, an elevation of eosinophils in the peripheral blood and broncho-alveolar lavage fluid, and rapid recovery. One of the 5 cases showed a re-elevation of eosinophils in the peripheral blood and broncho-alveolar lavage fluid after a smoking challenge test. It appears that one of the causes of acute eosinophilic pneumonia is beginning to smoke.

Acute Disease↗

PubMed1994

Eosinophils and eosinophil cationic protein in children with and without sensitization to inhalant allergens.

Eosinophil inflammation is a common feature of allergic disorders and particularly in allergic asthma interest has been paid to related markers. In a community-based survey of 10-year-old children, the association of eosinophil count (EC) and serum eosinophil cationic protein (ECP) with allergic sensitization, clinical history and exposure to mite allergen was studied. Relying on the results of skin prick tests, the children were divided to three groups: (1) children showing no sensitization to one of the seven inhalant allergens (n = 16); (2) children with sensitization to at least one of five non-mite allergens (n = 16); and (3) children with sensitization to mite allergens (n = 75). Clinical history of asthma and hay fever was ascertained using standardized questionnaires. EC in peripheral blood and serum ECP were measured on one single occasion. Prior to blood sampling, mite allergen exposure at home had been assessed by taking dust samples and measuring the mite antigen concentration by means of an enzyme immunoassay. Compared to group 1, higher ECs were obvious in group 2 (P = 0.037) and in group 3 (P = 0.0013). Regarding serum ECP, higher levels occurred in group 2 (P = 0.0033) as well as in group 3 (P = 0.0001) when comparing them to the reference group. Sensitized children with neither asthma, nor asthma-like symptoms, nor hay fever (n = 28) did not have significantly lower ECs and serum ECP levels than those with hay fever (n = 15; P = 0.09, P = 0.17) and those with asthma (n = 22; P = 0.69, P = 0.64).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Evidence for two platelet activating factor receptors on eosinophils: dissociation between PAF-induced intracellular calcium mobilization degranulation and superoxides anion generation in eosinophils.

We have compared platelet activating factor (PAF)-induced eosinophil peroxidase (EPO) release and intracellular calcium mobilization with superoxide anion (.O2-) generation from guinea pig eosinophils. EPO release and Ca2+ mobilization occurred at lower concentrations of PAF (EC50 values of 1.3 nM and 11.5 nM, respectively) while .O2- production was observed at higher concentrations (EC50 of 31.7 microM). Receptor characterization with the competitive PAF antagonist, WEB 2086, gave pA2 values of 8.5 and 8.3 for EPO enzyme release and rise in [Ca2+]i, respectively, and 5.8 for the .O2- production. In addition, PAF-induced degranulation and elevation of [Ca2+]i were dependent on extracellular Ca2+ whereas PAF-stimulated .O2- generation was dependent on the presence of extracellular Mg2+ ions. These results suggest the existence either of two subtypes of the PAF receptor or a single receptor that can exist in one of two affinity states on guinea pig eosinophils.

Animals↗

PubMed1981

Eosinophilic ureteritis? Regional ureteritis with marked infiltration of eosinophils.

The case of a thirty-seven-year-old man with eosinophilic granuloma of the ureter is discussed. Preoperative x-ray studies disclosed distal ureteric regional stenosis and moderate hydronephrosis with small stone shadows. A segmental ureterectomy and vesicoureteral neostomy were performed. Pathologic examination of the removed specimen revealed markedly infiltrated eosinophils of the ureteric wall. The literature is reviewed and the causation of eosinophilic granuloma discussed.

Adult↗

PubMed1994

Resonance Raman microspectroscopic characterization of eosinophil peroxidase in human eosinophilic granulocytes.

A resonance Raman microspectroscopic study is presented of eosinophil peroxidase (EPO) in human eosinophilic granulocytes. Experiments were carried out at the single cell level with laser excitation in Soret-, Qv-, and charge transfer absorption bands of the active site heme of the enzyme. The Raman signal obtained from the cells was almost exclusively due to EPO. Methods were developed to determine depolarization ratios and excitation profiles of Raman bands of EPO in situ. A number of Raman band assignments based on earlier experiments with isolated EPO have been revised. The results show that in agreement with literature on isolated eosinophil peroxidase, the prosthetic group of the enzyme in the (unactivated) cells is a high spin, 6-coordinated, ferric protoporphyrin IX. The core size of the heme is about 2.04 A. The proximal and distal axial ligands are most likely a histidine with the strong imidazolate character typical for peroxidases, and a weakly bound water molecule, respectively. The data furthermore indicate that the central iron is displaced from the plane of the heme ring. The unusual low wavenumber Raman spectrum of EPO, strongly resembling that of lactoperoxidase, intestinal peroxidase and myeloperoxidase, suggests that these mammalian peroxidases are closely related, and characterized by, as yet unspecified, interactions between the peripheral substituents and the protein, different from those found in other protoheme proteins.

Binding Sites↗

PubMed1993

The distribution of eosinophil cationic protein positive eosinophils in the nasal mucosa of the nasal allergy patients.

The relationship between the distribution of eosinophils and epithelial damage of the nasal mucosa in nasal allergy was investigated by means of hematoxylin and eosin staining and a technique of immunohistochemistry using the anti-human EG2 mouse monoclonal antibody that reacts with the secreted form of eosinophil cationic protein (ECP). Nasal mucosa tissue of 26 adult nasal allergy patients and of 24 adult non-allergic rhinitis patients was removed surgically. Eosinophilia in the nasal mucosa of the allergy group was greater than that in the non-allergy group. A great number of ECP positive eosinophils accumulating in the nasal mucosa of the allergy group were mostly degranulated at the superficial layer of the lamina propria. Desquamation of the epithelium was observed mainly in the area of eosinophilia with degranulation of the secreted form of ECP in the nasal allergy group.

Adult↗

PubMed1999

3-Bromotyrosine and 3,5-dibromotyrosine are major products of protein oxidation by eosinophil peroxidase: potential markers for eosinophil-dependent tissue injury in vivo.

Detection of specific reaction products is a powerful approach for dissecting out pathways that mediate oxidative damage in vivo. Eosinophil peroxidase (EPO), an abundant protein secreted from activated eosinophils, has been implicated in promoting oxidative tissue injury in conditions such as asthma, allergic inflammatory disorders, cancer, and helminthic infections. This unique heme protein amplifies the oxidizing potential of H2O2 by utilizing plasma levels of Br- as a cosubstrate to form potent brominating agents. Brominated products might thus serve as powerful tools for identifying sites of eosinophil-mediated tissue injury in vivo; however, structural identification and characterization of specific brominated products formed during EPO-catalyzed oxidation have not yet been reported. Here we explore the role of EPO and myeloperoxidase (MPO), a related leukocyte protein, in promoting protein oxidative damage through bromination and demonstrate that protein tyrosine residues serve as endogenous traps of reactive brominating species forming stable ring-brominated adducts. Exposure of the amino acid L-tyrosine to EPO, H2O2, and physiological concentrations of halides (100 mM Cl-, </=100 microM Br-) produced two new major products with distinct retention times on reverse phase HPLC. The products were identified as 3-bromotyrosine and 3, 5-dibromotyrosine by electrospray ionization mass spectrometry and multinuclear (1H and 15N) NMR spectroscopy. Formation of the ring-brominated forms of the amino acid occurred readily at neutral pH with the enzymatic system and a variety of reactive brominating species, including HOBr/OBr-, N-bromoamines, and N,N-dibromoamines. Addition of primary amines (e.g., Nalpha-acetyllysine and taurine) to L-tyrosine exposed to either HOBr/OBr- or the EPO-H2O2-Br- system enhanced phenolic ring bromination, suggesting N-bromoamines are preferred brominating intermediates in these reactions. Reduction of N-bromoamines (e.g., Nalpha-acetyl,Nepsilon-bromolysine) by L-tyrosine was shown to result in the loss of reactive halogen with a near stoichiometric increase in the level of tyrosine ring bromination (i.e., carbon-bromine bonds). Although both EPO and MPO could use Br- to halogenate protein tyrosine residues in vitro, only EPO effectively brominated the aromatic amino acid at physiological levels of halides and H2O2. Collectively, these results suggest that 3-bromotyrosine and 3,5-dibromotyrosine are attractive candidates for serving as molecular markers for oxidative damage of proteins by reactive brominating species in vivo. They also suggest that in biological mixtures where amine groups are abundant, the trapping of EPO-generated HOBr/OBr- as N-bromoamines will serve to effectively "funnel" reactive brominating equivalents to stable ring-brominated forms of tyrosine.

Animals↗

PubMed2001

Urinary leukotriene E(4), eosinophil protein X, and nasal eosinophil cationic protein are not associated with respiratory symptoms in 1-year-old children.

BACKGROUND: Eosinophilic airways inflammation forms the pathophysiologic basis for a proportion of children at risk of developing recurrent wheezing. Early preventive measures and/or anti-inflammatory treatment may be guided by the identification of such children. We aimed to study the relationship between respiratory symptoms and indirect markers of airway inflammation. METHODS: We measured eosinophil protein X (EPX) and leukotriene E(4) (LTE(4)) in urine, as well as eosinophil cationic protein (ECP) in nasal lavages, in a random sample of 1-year-old children with a family history of atopy who participated in an international multicenter study on the prevention of allergy in Europe. For urine analyses, 10 children with upper respiratory illness and 19 healthy children without a family history of atopy were also enrolled. Endogenous urinary LTE(4) was separated by HPLC and determined by enzyme immunoassay with a specific antibody. The concentrations of nasal ECP and urinary EPX were determined by RIA analysis. RESULTS: One hundred and ten children (mean age: 1.05+/-0.1 years) were enrolled. Prolonged coughing during the first year of life was reported in 29 children, wheezy breathing in 17 children, and dry skin in 33 children. A doctor's diagnosis of wheezy bronchitis was given to 17 children. Sensitization to dust mites (specific IgE > or =1.43 ML/units) was detected in two children. Children with a doctor's diagnosis of atopic dermatitis within the first 12 months of life (n=6) had significantly higher urinary EPX than children without this (66.7 vs 30.1 microg/mmol creatinine, P=0.01). Urinary excretion of EPX and LTE4 showed a weak correlation (r=0.22, P=0.02). There were no significant differences in urinary excretion of EPX and LTE(4) or nasal ECP between children with and without respiratory symptoms (P>0.1). CONCLUSIONS: At the age of 1 year, urinary EPX is increased in children with atopic dermatitis. With regard to respiratory symptoms, urinary and nasal inflammatory parameters are not helpful in characterizing the phenotype of a single patient.

Animals↗

PubMed2003

Stimulation of P2 purinergic receptors induces the release of eosinophil cationic protein and interleukin-8 from human eosinophils.

1. Extracellular nucleotides are the focus of increasing attention for their role as extracellular mediators since they are released into the extracellular environment in a regulated manner and/or as a consequence of cell damage. 2. Here, we show that human eosinophils stimulated with different nucleotides release eosinophil cationic protein (ECP) and the chemokine interleukin 8 (IL-8), and that release of these two proteins has a different nucleotide requirement. 3. Release of ECP was triggered in a dose-dependent manner by ATP, UTP and UDP, but not by 2'-&3'-o-(4-benzoyl-benzoyl)adenosine 5'-triphosphate (BzATP), ADP and alpha,beta-methylene adenosine 5' triphosphate (alpha,beta-meATP). Release of IL-8 was triggered by UDP, ATP, alpha,beta-meATP and BzATP, but not by UTP or ADP. Pretreatment with pertussis toxin abrogated nucleotide-stimulated ECP but not IL-8 release. 4. Release of IL-8 stimulated by BzATP was fully blocked by the P2X(7) blocker KN-62, while release triggered by ATP was only partially inhibited. IL-8 secretion due to UDP was fully insensitive to KN-62 inhibition. 5. Priming of eosinophils with GM-CSF increased IL-8 secretion irrespectively of the nucleotide used as a stimulant. 6. It is concluded that extracellular nucleotides trigger secretion of ECP by stimulating a receptor of the P2Y subfamily (possibly P2Y(2)), while, on the contrary, nucleotide-stimulated secretion of IL-8 can be due to activation of both P2Y (P2Y(6)) and P2X (P2X(1) and P2X(7)) receptors.

Blood Proteins↗

PubMed1986

Biochemical and functional similarities between human eosinophil-derived neurotoxin and eosinophil cationic protein: homology with ribonuclease.

Eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) were isolated from lysates of human eosinophil granules by gel filtration and ion exchange chromatography on heparin-Sepharose. Radioimmunoassay, using monoclonal antibodies, of fractions from the heparin-Sepharose chromatography showed one peak of EDN activity and two peaks of ECP activity (termed ECP-1 and ECP-2). EDN, ECP-1, and ECP-2 each exhibited heterogeneity in charge and molecular weight when analyzed by two-dimensional nonequilibrium pH gradient electrophoresis and NaDodSO4/PAGE. Digestion of EDN with endoglycosidase F (endo F) decreased its molecular weight and charge heterogeneity. Thus, END likely contains a single complex oligosaccharide. Endo F digestion of ECP-1 and ECP-2 decreased the molecular weight of both polypeptides, indicating that both likely contain at least one complex oligosaccharide. Amino acid sequence analyses showed that ECP-1 and ECP-2 are identical from residue 1 through residue 59 and that the sequences of EDN and ECP are highly homologous (37 of 55 residues identical). Both EDN and ECP NH2-terminal sequences showed significant homology to RNase, especially in regions of the RNase molecule involved in ligand binding. EDN, ECP-1, and ECP-2 had neurotoxic activity, causing the Gordon phenomenon at doses down to 0.15 micrograms when injected into the cisterna magna; the proteins were comparable in their activities. These results indicate that EDN and ECP are related proteins and suggest that they derived from genes associated with the RNase family.

Amino Acid Sequence↗

PubMed2002

Epithelial cells in nasal fluids from patients with allergic rhinitis: how do they relate to epidermal growth factor, eosinophils and eosinophil cationic protein?

The nasal epithelium protects the underlying tissue from damage. Epithelial cell growth is controlled by epidermal growth factor (EGF) and is possibly affected by toxic proteins, e.g. eosinophil cationic protein (ECP). The aims of this study were to examine nasal fluid epithelial cell counts and their relations to EGF, eosinophils and ECP in 23 patients with seasonal allergic rhinitis and 20 healthy controls. Nasal fluid epithelial cell counts were lower in patients than in controls. EGF levels did not differ between patients and controls, and correlated with epithelial cell counts in controls but not in patients. Eosinophils and ECP were higher in patients than in controls, but did not correlate with epithelial cell counts. The role of growth factors, such as EGF, in regulating epithelial cells merits further study.

Adolescent↗

PubMed2000

The release of eosinophil chemotactic activity and eosinophil chemokinesis inhibitory activity by mononuclear cells from atopic asthmatic and non-atopic subjects.

The goal of our study was to assess the chemotactic activity for eosinophils (ECA) and neutrophils (NCA) and histamine releasing activity (HRA) in crude supernatants of mononuclear cells in monosensitized atopic asthmatics and healthy controls. Chemotactic activity for ECA and neutrophils was measured in supernatants of cultured mononuclear cells with modified Boyden's chamber and HRA was assessed on healthy donor basophils. With respect to ECA generation two distinct subgroups of subjects were distinguished: releasers [ECA (+)] and non-releasers [ECA (-)]. In atopic and non-atopic ECA (+) the mean ECA index was 3.78 +/- 0.49 and 2.47 +/- 0.27 respectively (P > 0.05). Supernatants from the remaining subjects (seven of 22 atopic and five of 11 non-atopic) did not express ECA, but revealed significant inhibitory activity for chemokinesis of eosinophils (mean chemotactic index 0.25 +/- 0.16 and 0.48 +/- 0.22 for atopic and non-atopic non-releasers respectively). Stimulation with antigen of MNC from atopic and with PHA from non-atopic ECA (-) restored cells ability to release ECA. Sephadex gel chromatography revealed that supernatants of MNC contained chemotactic and chemokinesis inhibitory activity in different fractions. The spontaneous productions of NCA and HRA by mononuclear cells was similar in ECA releasers and non-releasers, although the HRA was higher following stimulation with PHA in the non-atopic ECA (+) subgroup. Our study demonstrated, for the first time, that MNC are capable of generating not only chemotactic activity but also chemokinesis inhibitory activity for eosinophils.

Adult↗

PubMed1980

Eosinophil response in guinea pig skin to a low molecular weight eosinophil chemotactic factor extracted from livers of mice with schistosomiasis.

A low-molecular weight eosinophil chemotactic factor (ECF-G), isolated and partially purified from livers of mice with schistosomiasis, was injected intradermally into guinea pigs. Biopsies obtained were studied for inflammatory cell accumulation in the injected sites and compared with those in the control sites injected with phosphate buffered saline. Tissue eosinophilia was seen as early as 1 hr after injection of ECF-G, but not in the control site. The increase of eosinophilia appeared biphasic with peaks at 6 and 24 hr. Mast cells increased in both ECF-G and saline injected sites and the increase was still found at 120 hr after injection. Neutrophils also increased in both ECF-G and saline injected sites but disappeared within 48 hr. These findings indicate that ECF-G is a tissue and species nonspecific eosinophil chemotactic factor, and injection of ECF-G initiates interaction of eosinophils and mast cells in the skin.

Animals↗

PubMed1983

Effects of trichinellosis on levels of eosinophils, eosinophil major basic protein, creatine kinase and basophils in the guinea pig.

The effects of multiple infections with Trichinella spiralis on the levels of eosinophil major basic protein (MBP), creatine kinase (CK), and leucocytes were studied in the guinea pig. Plasma MBP levels increased after each of four successive infections with T. spiralis. The times of peak elevations in MBP levels and eosinophilia correlated significantly, and both peaks occurred earlier with increased infection dose. CK levels were elevated most dramatically in the primary infection. A direct correlation between peak CK values and larval dose was observed, and the peak occurred earlier with larger larval doses. A dose-dependent basophilia was observed in the primary infection and, like the eosinophil response, basophilia occurred earlier and was markedly enhanced after the second infection. The elevations in MBP levels and eosinophil counts persisted into the third and fourth infections; the basophil response persisted only through the third infection.

Animals↗

PubMed1981

Hemodialysis-induced increase in serum lactoferrin and serum eosinophil cationic protein as signs of local neutrophil and eosinophil degranulation.

Transient reduction in circulating polymorphonuclear granulocytes and eosinophils were observed early in hemodialysis. About a threefold increase in serum-lactoferrin occurred 2 h from the start of hemodialysis. Increments of the serum levels of eosinophil cationic protein (ECP) were observed as early as 1 h after initiation of hemodialysis, reaching maximum levels (about a fourfold increase from initial levels) 1 h later. When fresh blood was circulated through a dialyzer without having a patient in the circuit considerable increases of lactoferrin and ECP were also found. The intracellular contents of lactoferrin and ECP in granulocytes isolated from peripheral blood were unaffected throughout the dialysis period. Sera obtained at different times during dialysis induced no release of granular proteins from isolated granulocytes in vitro. The raised serum concentrations of lactoferrin and ECP during dialysis suggest that a local degranulation of neutrophils and eosinophils may take place probably in the dialyzer.

Adult↗

PubMed1997

Relationship between activated eosinophils of the bronchial mucosa and serum eosinophil cationic protein in atopic asthma.

We biopsied the bronchial mucosa of 20 atopic bronchial asthma patients and measured their serum eosinophil cationic protein (ECP) levels as a means of assessing whether serum ECP could be as a marker of airway eosinophil inflammation. We also investigated the relationship between serum ECP levels and airway hypersensitivity, pulmonary function, peak expiratory flow (PEF) and attack scores. EG2 monoclonal antibody was used to immunostain bronchial mucosal tissue, and positive cells were expressed as the number of positive cells per square millimeter of lamina propria mucosae. A significant correlation was found between bronchial mucosa EG2+ cell counts and serum ECP levels (r = 0.66, p < 0.01), but no clear relationships were detected between serum ECP levels and airway hypersensitivity, pulmonary function, PEF or attack scores. Based on the above findings, serum ECP levels reflect airway eosinophilic inflammation, but ECP levels must be considered in combination with other parameters in relation to the pathophysiology of asthma.

Adolescent↗

PubMed1975

[Chronic eosinophilic leukemia with eosinophilic granulomas of the lung (author's transl)].

For the first time a report is given on a case of chronic eosinophilic leukemia with occurence of eosinophilic pulmonary granulomas. Even after enucleation of the granulomas eosinophilia remained in the peripheral blood and in the bone marrow, and over a period of 6 years lay at a value of above 50% of the granulocytes. The illness ended with sudden increase in the number of myeloblasts. The autopsy revealed destruction of the bone marrow by myeloblasts, immature and mature eosinophilic granulocytes as well as infiltration of the heart, liver, spleen and kidneys. On the basis of histological, cytological and histochemical examinations of the granulomas, the peripheral blood and the organs after dissection, particularly of the bone marrow, there was good reason to assume common pathogenesis of these changes; it was not however possible to completely exclude an allergically generated cause.

Autopsy↗