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Query: UNIPROT:P06889 (Mol)
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Eosinophilic enteritis and eosinophilia, in addition to muscular dystrophy and occasionally liver necrosis, were experimentally induced in male Sprague-Dawley rats with a vitamin E- and selenium-deficient diet (basal diet) for 9 weeks. Cecum and ileum were affected more frequently and severely than other segments of the gastrointestinal tract. Eosinophils were multifocally or diffusely distributed in the intestinal wall but were most severe in the muscular layer and in the submucosa. Eosinophils were also present in stomach, liver with massive hepatocellular necrosis, and skeletal muscle with marked myonecrosis. Eosinophilic enteritis and eosinophilia were not observed in rats fed the basal diet supplemented with either vitamin E (100 or 200 ppm) or selenium (0.1 or 1.0 ppm). Eosinophilic enteritis, eosinophilia, and muscular dystrophy regressed when vitamin E- and selenium-deficient rats were subsequently fed either the vitamin E- or selenium-supplemented diet for 4-5 weeks. These findings suggest that vitamin E and selenium deficiency may play a role in the development of a diffuse type of eosinophilic enteritis and eosinophilia.
Exp Mol Pathol 1988 Apr
PMID:Induction of eosinophilic enteritis and eosinophilia in rats by vitamin E and selenium deficiency. 335 Jan 41

The late-phase of allergic asthma is characterized by infiltration of the airway with eosinophils within 6 h of mast cell activation. Pro-eosinophilic/pro-allergic (TH2) cytokines, originally described as T-lymphocyte products, have recently been ascribed to mast cells as well. To date, however, it is unknown if TH2 cytokine gene expression by the human mast cells is subject to receptor-mediated regulation analogous to that of T-cells, and if messenger RNA (mRNA) expression results in protein secretion occurring in a temporal context consistent with the late-phase response. We examined interleukin-4 (IL-4), IL-5, and IL-6 mRNA expression induced by anti-IgE activation of human lung explants as assessed using reverse transcription/polymerase chain reaction (RT-PCR). Anti-IgE stimulation resulted in rapid and sustained upregulation of IL-5 message, but did not have analogous effects on IL-4 or IL-6. Using quantitative-competitive PCR, we demonstrated that 100 ng of total cellular RNA from human lung contained 1 fg of IL-5 mRNA; this increased to 100 fg 4 h after anti-IgE activation. The source of the anti-IgE-enhanced IL-5 mRNA is likely the mast cell itself, as anti-CD3 activation of lung led to a dissimilar array of cytokine expression. In addition, human lung mast cells purified to near homogeneity expressed IL-5 mRNA after activation, as shown by both RT-PCR and in situ hybridization. In both lung fragments and purified human lung mast cells, the modulation of IL-5 mRNA expression preceded the secretion of IL-5 protein, detected as early as 4 h after activation. Neither isolated purified mast cells nor purified peripheral blood T cells could be induced to secrete detectable amounts of IL-5 protein when activated only with antibodies against IgE or CD3-T cell receptor complex, respectively. However, mast cells (n = 4) and T cells (n = 6) cultured at comparable concentrations (4 x 10(6)/ml) activated through their respective antigen receptors in the presence of phorbol ester yielded comparable IL-5 production (253 +/- 126 pg/ml versus 183 +/- 75 pg/ml, mean +/- SE). We conclude that mast cells are analogous to T cells in the requirement of co-stimuli for the production of IL-5 protein. Moreover, the rapid kinetics of IgE-mediated IL-5 transcription and protein elaboration are consistent with a primary role for mast cell activation directly leading to late-phase airway eosinophilia.
Am J Respir Cell Mol Biol 1995 Dec
PMID:Human lung mast cell IL-5 gene and protein expression: temporal analysis of upregulation following IgE-mediated activation. 757 4

The ovalbumin-sensitized guinea pig is commonly used as a small animal model of allergic asthma. This animal model exhibits many of the hallmark characteristics observed in patients afflicted with asthma including nonspecific airway hyperreactivity, airway eosinophilia, early and late phase bronchoconstriction, and plasma extravasation into the airways. In addition, mucous hypersecretion in the airways of asthmatic patients is thought to be responsible for the plugging of distal airways and to contribute to the morbidity and mortality associated with the disease process. In this study we examined whether the allergic guinea pig model exhibits an increase in airway high molecular weight glycoconjugate (HMWG) secretion in response to an antigen challenge and whether dexamethasone exerts any modulatory effects upon the response. Ovalbumin (OVA) -sensitized guinea pigs were challenged with OVA 2 wk following the initial exposure. Trachobronchoalveolar lavages (TBAL) were performed, and the samples were assayed for total eosinophil cell number, eosinophil peroxidase activity (EPO), and both acidic and neutral HMWG content. Morphometric analysis of mucous-containing cells was also performed on tissue sections prepared from the trachea, mainstem bronchus, and three lobes of the left lung. Within 24 h of an antigen challenge, TBAL samples obtained from the allergic guinea pigs exhibited increases in eosinophil cell number, measured EPO enzyme activity, and acidic HMWG content compared to TBAL samples prepared from vehicle-exposed animals. These antigen-induced changes were dependent on the concentration of aerosolized OVA administered. Exposing the animals to 0.3% OVA provoked a 6.23-fold increase in airway eosinophils, 15-fold elevation in TBAL EPO enzyme activity, and 175% increase in TBAL acidic HMWG. No significant changes in TBAL neutral HMWG were measured. The changes in measured EPO activity correlated with the levels of acidic HMWG found in the TBAL samples (r = 0.73, P < or = 0.001). The measured increase in TBAL acidic HMWG was time dependent and was found to be maximal at 2 h post-antigen challenge. Morphometric analysis of Alcian blue (pH 2.5) -stained airway sections showed a decline in stored mucosubstances following the antigen exposure, supporting the notion that the allergic guinea pig model exhibits a mucosecretory component. Pretreating the animals with dexamethasone attenuated the antigen-induced release of HMWG and changes in measured EPO activity. In conclusion, these data indicate that the allergic guinea pig may be a useful model for examining the neural and cellular mechanisms underlying mucus hypersecretion in individuals afflicted with bronchial asthma.
Am J Respir Cell Mol Biol 1995 Aug
PMID:Effect of dexamethasone on antigen-induced high molecular weight glycoconjugate secretion in allergic guinea pigs. 762 83

Interleukin 5 (IL-5) is a T-cell lymphokine known to stimulate development, functional activity, and in vitro survival of eosinophils. Tissue and blood eosinophilia occurring during allergic responses of the immune system are potentially mediated by IL-5 secreting T-cells. To test this hypothesis a series of allergen-specific T-cell clones were established from peripheral blood and skin lymphocytes of patients with atopic dermatitis and house dust mite sensitization. In addition, alloreactive T-cell clones were also prepared from peripheral blood lymphocytes of healthy donors. Cloned T-cells were analyzed for IL-5 mRNA expression and IL-5 secretion by means of in vitro gene amplification using the reverse transcriptase polymerase chain reaction and IL-5 specific oligonucleotide hybridization, as well as IL-5-specific ELISA. A majority of allergen-specific long-term cultured T-cell clones (84%) of different donors and of either phenotype (CD8+ or CD4+) disclosed IL-5 transcripts on stimulation with lectins. Almost all clones exhibiting IL-5 transcripts also released immunoreactive IL-5 protein into their culture supernatants. In contrast, only 2% of alloreactive T-cell clones obtained from healthy donors and none of alloreactive T-cell clones of one atopic patient investigated expressed detectable amounts of IL-5 mRNA in response to lectin stimulation, all of whom were CD4+. These results suggest that eosinophilia observed in allergic responses in the peripheral blood and in tissues at the site of induced late-phase cutaneous reaction may be associated with IL-5 release by allergen-specific T-cells.
J Mol Med (Berl) 1995 Feb
PMID:Interleukin 5 expressing allergen-specific T-lymphocytes in patients with house dust mite sensitization: analysis at a clonal level. 941 Apr 77

Mast cells are important effector cells in IgE-mediated acute allergic reactions. Mast cells also produce cytokines such as interleukin (IL)-3, IL-4, IL-5, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) that regulate the function of eosinophils and the development of a late-phase inflammatory response to antigen challenge. To evaluate the role of mast cells on the development of IgE-mediated allergic pulmonary eosinophilia in vivo, we compared the eosinophil infiltration into lungs of mast cell deficient mice (WBB6F1/J-W/Wv) with their congenic normal littermates (W/W+). Mice were sensitized with alum-precipitated ovalbumin and challenged with aerosolized ovalbumin on day 12 after sensitization. Bronchoalveolar lavage (BAL) fluid, lung tissue biopsies, and blood samples were collected after ovalbumin challenge. Eosinophil numbers in the BAL and lung tissue, lung eosinophil peroxidase (EPO) activity and serum levels of IgE and IgG1 were measured. In sensitized W/W+ mice, there were increased numbers of eosinophils in the BAL fluid and lung tissue, and EPO levels were increased after ovalbumin challenge. Ovalbumin challenge of sensitized mast-cell-deficient mice produced fewer numbers of eosinophils in the BAL fluid and lungs, and EPO levels were also reduced compared with their challenged congenic littermates. On the other hand, levels of serum IgE and IgG1 were not different between W/Wv mice and their congenic littermates.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1995 Apr
PMID:Mast cells modulate allergic pulmonary eosinophilia in mice. 769 19

Aeroallergen-induced eosinophilia in actively sensitized guinea pigs was used as a marker of bronchial inflammation in this study. Drugs were administered p.o. therapeutically, i.e., four hours after aeroallergen challenge. Allergic bronchial eosinophilia in guinea pigs was sensitive to dexamethasone. Thus, the therapeutic approach appears to be a reliable, predictable, and sensitive for the evaluation and selection of potential bronchial anti-inflammatory compounds. PAF-antagonists (WEB-2086, WEB-2170, and E-6123) and a 5-lipoxygenase inhibitor (E-6080) did not influence allergen-induced eosinophil infiltration in the bronchoalveolar lavage fluid. These observations seem to suggest that therapeutic administration of PAF antagonists and leukotriene synthesis inhibitors exert little or no inhibitory effect on the progression of late-phase allergic bronchial inflammation in this model.
Res Commun Mol Pathol Pharmacol 1994 Oct
PMID:Effect of PAF-antagonists on aeroallergen-induced bronchial eosinophilia in guinea pigs: a therapeutic approach. 785 Feb 58

Guinea pigs sensitized to ovalbumin develop airway eosinophilia and bronchial hyperresponsiveness to acetylcholine and histamine 24 h after ovalbumin challenge. We have used two different antibodies to the leukocyte integrin CD18 (R15.7 and 6.5E) to study the link between eosinophilia and the development of bronchial hyperresponsiveness. In this model, both these antibodies reduced, to a similar degree, the number of eosinophils recovered from bronchoalveolar lavage fluid, although the eosinophil numbers in lung tissue were not reduced. However, only R15.7 reduced bronchial hyperresponsiveness. The results suggest that the CD18 integrin is involved in the recruitment of leukocytes to the airways, but increased numbers of eosinophils in lavage fluid are not an essential correlate of bronchial hyperresponsiveness in this model.
Am J Respir Cell Mol Biol 1994 Sep
PMID:The effects of two anti-CD18 antibodies on antigen-induced airway hyperresponsiveness and leukocyte accumulation in the guinea pig. 791 97

To investigate the mechanism of eosinophilia in patients with eosinophilic pleural effusions, we measured the activities of eosinophil colony-stimulating factor (Eo-CSF) and stimulating factor for eosinophil survival in the eosinophilic pleural fluids of six patients (two with tuberculous pleuritis, two with drug allergy, and one each with chronic eosinophilic pneumonia and pleuritis associated with rheumatoid arthritis). The number of eosinophil colonies formed by the pleural fluid of patients with eosinophilic pleural effusions significantly exceeded that of control patients with noneosinophilic pleural effusions (7.5 +/- 1.9 colonies/10(5) bone marrow cells, n = 6, versus 0.3 +/- 0.1 colonies/10(5) bone marrow cells, n = 6, P < 0.01). Similarly, eosinophil survival evaluated on day 4 of culture with pleural fluid of patients with eosinophilic pleural effusions significantly exceeded that of patients with noneosinophilic pleural effusions (83.9 +/- 9.8% versus 46.1 +/- 11.2%, P < 0.001). Both activities were inhibited mainly by anti-IL-5 antibody and partially by anti-GM-CSF antibody and anti-IL-3 antibody. Mononuclear cells obtained from eosinophilic pleural fluid released the activities of Eo-CSF and stimulating factor for eosinophil survival in vitro. These findings suggest that GM-CSF, IL-5, and IL-3 are important to eosinophil accumulation in pleural cavity as stimulators of proliferation and survival of eosinophils.
Am J Respir Cell Mol Biol 1993 Jun
PMID:Factors that stimulate the proliferation and survival of eosinophils in eosinophilic pleural effusion: relationship to granulocyte/macrophage colony-stimulating factor, interleukin-5, and interleukin-3. 832 45

Stimulated migration of eosinophils out of the bloodstream and into the lung is key in the development of tissue eosinophilia and inflammation in asthma. Platelet-activating factor (PAF) has been implicated as an important inflammatory mediator in asthma pathogenesis in part because of its chemotactic capacity. We therefore studied the ability of PAF to induce human peripheral blood eosinophil migration through naked filters and human umbilical vein endothelial cells (HUVECs) cultured on these filters. PAF induced eosinophil migration through both barriers in a time-dependent fashion, with maximal eosinophil migration occurring at 180 min. Significant eosinophil migration was observed at PAF concentration > or = 0.1 microM and was dose dependent up to 10.0 microM. No significant differences in eosinophil chemotactic responses were noted between naked filter and HUVEC barriers. The PAF receptor antagonist, WEB 2086, inhibited (> 85%) eosinophil transendothelial migration when co-incubated with PAF or when used as a pretreatment of either the eosinophils or HUVECs. However, WEB 2086 pretreatment of HUVECs did not inhibit PAF-induced neutrophil transendothelial migration, nor did it affect leukotriene B4-induced neutrophil or eosinophil transendothelial migration. Thus, the data indicate that the endothelial cell plays an important role in PAF-induced eosinophil inflammatory processes. Moreover, these data suggest that PAF's pathogenic role in asthma may in part be due to its ability to stimulate eosinophil migration across endothelial barriers and into the airways.
Am J Respir Cell Mol Biol 1993 Jan
PMID:Platelet-activating factor-induced human eosinophil transendothelial migration: evidence for a dynamic role of the endothelium. 838 Feb 50

It is well known that antigen challenge of sensitized subjects can induce an immediate and late asthmatic response, airway eosinophilia, and hyperreactivity. Using our modified guinea pig asthma model, we investigated the superoxide anion generation from eosinophils and macrophages recovered from bronchoalveolar lavage (BAL) 24 h after antigen (ovalbumin) challenge. We also investigated the effect of formoterol, a new long-acting selective beta 2-agonist, on these functions. Antigen challenge increased the total cell counts and the ratio of eosinophils in BAL. Eosinophils and macrophages were collected using discontinuous density centrifugation. Antigen challenge enhanced superoxide anion generation from eosinophils, from 5.39 +/- 1.08 to 13.19 +/- 1.95 nmol 60 min after phorbol myristate acetate (PMA) (1 ng/ml) activation, and 0.22 +/- 0.49 to 3.34 +/- 1.67 nmol 40 min after platelet-activating factor (PAF) (10(-6) M) activation. Formoterol treatment before antigen challenge prevented these enhancements. Superoxide anion generation from macrophages was also enhanced by antigen challenge, from 6.57 +/- 0.76 to 10.66 +/- 0.88 nmol 60 min after PMA activation, and 4.20 +/- 1.17 to 6.63 +/- 0.64 nmol 60 min after PAF activation. Formoterol, however, failed to inhibit enhancement of superoxide anion generation from macrophages. These results show antigen challenge of sensitized guinea pigs induces an increase of eosinophils and macrophages in BAL and enhances the functional characteristics of both cells. Formoterol had inhibitory effects on the enhancement of superoxide anion generation from eosinophils but did not have this effect on macrophages.
Am J Respir Cell Mol Biol 1993 May
PMID:Effect of formoterol on superoxide anion generation from bronchoalveolar lavage cells after antigen challenge in guinea pigs. 838 28


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