Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T cell-replacing factor (TRF)/IL-5 is a glycosylated polypeptide that acts as a key factor for B cell growth and differentiation. Since IL-5 action is probably mediated by specific cell surface receptor(s), we have characterized the binding of IL-5 to cells using biosynthetically [35S]methionine-labeled IL-5 and 125I-IL-5 that had been prepared using Bolton-Hunter reagent. The radiolabeled IL-5 binds specifically to BCL1-B20 (in vitro line) (a murine chronic B cell leukemic cell line previously shown to differentiate into IgM-secreting cells in response to IL-5) within 10 min at 37 degrees C. There are two classes of binding sites with high affinity (Kd = 66 pM) and low affinity (Kd = 12 nM) for IL-5 and an average number of binding sites for high affinity and for low affinity were 400 and 7,500 per cell, respectively. The specificity of binding of radiolabeled IL-5 has been confirmed by demonstrating that only unlabeled IL-5 and anti-IL-5 mAb but not by IL-1, IL-2, IL-3, IFN-gamma, and GM-CSF inhibit radiolabeled IL-5 binding to BCL1-B20 cells. Treatment of surface-bound radiolabeled IL-5 with bivalent crosslinkers identified a membrane polypeptide of Mr 46,500 to which IL-5 is crosslinked. A variety of cell types have been surveyed for the capacity to bind specifically radiolabeled IL-5 with high affinity. BCL1 cells MOPC104E (murine myeloma cell line) expressed IL-5-R, whereas BAL. 17 and L10 A (B cell lymphoma) did not. T cell line, mastocytoma cell line, or macrophage tumor cell line did not display detectable levels of IL-5-R. were hardly detectable on normal resting B cells but were expressed on LPS-activated B cells, fitting the function of IL-5 that acts on activated B cells for their differentiation into Ig-secreting cells. Intriguingly, early B cell lines (J-87 and T-88) that grow in the presence of IL-5 expressed significant but low numbers of high-affinity binding sites for IL-5. The biological effects of IL-5 were mediated by high-affinity binding sites. The identification and characterization of IL-5-R should provide new insight into the apparent diverse biological activities of IL-5.
 ...
PMID:Receptors for T cell-replacing factor/interleukin 5. Specificity, quantitation, and its implication. 326 7

To investigate the role of IL-5 in airway hyperreactivity and pulmonary eosinophilia, we used a model of allergic asthma in guinea pigs and a neutralizing monoclonal antibody (TRFK-5) directed against murine IL-5. Sensitized guinea pigs were challenged with 1% ovalbumin (OVA) aerosol and assessed for airway eosinophilia (by bronchoalveolar lavage [BAL] and histologic evaluation of airway tissue) and bronchoconstrictor responsiveness to substance P (SP) (as RL100 and Cdyn40) 24 h later. OVA challenge of sensitized animals caused a significant increase in airway responsiveness to SP, with a 4.9-fold decrease in RL100 and a 4.7-fold decrease in Cdyn40. Accompanying this increased sensitivity to SP was a 9-fold increase in eosinophils recovered in BAL and a 4- to 5-fold increase in eosinophils in intrapulmonary bronchial tissue. Intraperitoneal treatment with 10 mg/kg of the IL-5 antibody 2 h before OVA challenge blocked BAL and lung tissue increases in eosinophils but had no effect on the development of airway sensitivity to SP. In contrast, similar treatment with 30 mg/kg of this antibody blocked OVA-induced increased sensitivity to SP as well as BAL and lung tissue eosinophilia. These data suggest a critical and possibly independent role for IL-5 in allergic airway hyperresponsiveness and the accumulation of eosinophils within the lung of the guinea pig.
 ...
PMID:Inhibitory effect of the TRFK-5 anti-IL-5 antibody in a guinea pig model of asthma. 750 92

Increasing evidence suggests a role for activated T cells and cytokines in the regulation of eosinophilic inflammation in asthma. In this study, we investigated the distribution of leukocytes, lymphocytes, their activation state, and the cytokine profile in BAL from 10 atopic asthmatics with positive skin prick tests and elevated specific IgE levels to birch or grass pollen. Using segmental allergen challenge, 250 PNU of the appropriate allergen or saline were instilled into different segments, which were lavaged 10 min (10 min) and 18 h (18 h) after allergen challenge or 18 h after saline challenge (C). In peripheral blood the number of neutrophils and activated IL-2R+/CD4+ T cells increased significantly 18 h after allergen provocation; there was no change in eosinophils, other leukocytes, or lymphocyte subsets. In contrast, numbers of eosinophils, neutrophils, and IL-2R+/CD4+ T cells increased significantly in BAL samples at 18 h. The numbers of neutrophils and eosinophils were not significantly different in the lavage performed at 10 min and at C. Analysis of cytokines in concentrated BAL fluid revealed significantly increased levels of IL-5, IL-2, IL-1, TNF-alpha, IL-6, IL-8, and GM-CSF, but not of IL-4 and IFN-gamma at 18 h compared with those at C and at 10 min. The correlation between IL-5 levels, eosinophil numbers, and activated T cells supports a role for T-cell-derived IL-5 in causing tissue eosinophilia in allergic asthma.
 ...
PMID:T cells and cytokines in bronchoalveolar lavage fluid after segmental allergen provocation in atopic asthma. 769 73

T-lymphocyte (T-LC)-derived cytokines have been implicated in asthma pathogenesis. Activation of peripheral blood CD4 but not CD8 T-LC and a Th2-type pattern of elevated cytokine mRNA expression in BAL fluid T-LC have been observed in asthmatics, but the principal source (CD4 or CD8 T-LC) of these cytokines is unknown. Our objective was to measure expression of Th1- and Th2-type cytokine mRNA and spontaneous secretion of IL-3, IL-5, and GM-CSF by peripheral blood CD4 and CD8 T-LC from asthmatics before and after oral glucocorticoid therapy and non-asthmatic controls. We used in situ hybridization to detect mRNA expression in isolated CD4 and CD8 T-LC, and an in vitro eosinophil survival assay to detect secretion of IL-3, IL-5, and GM-CSF in T-LC culture supernatants. Comparing the asthmatics with the controls, elevated percentages of CD4 T-LC expressed mRNA encoding IL-5, IL-4, and GM-CSF (P < 0.02) but not IL-3, IL-2, or IFN-gamma. In CD8 T-LC, mRNA expression was generally low with no significant differences between the groups. In the asthmatics, the percentages of CD4 T-LC expressing IL-5 mRNA correlated with disease severity and the numbers of peripheral blood eosinophils (P < 0.01). Culture supernatants of asthmatic CD4 but not CD8 T-LC exhibited significantly higher (P = 0.0003) eosinophil survival-prolonging activity compared with controls, in which low activity was detected. Inhibition with anti-cytokine antibodies suggested that GM-CSF, and to a lesser extent IL-5 and IL-3, could account for this activity. After oral glucocorticoid therapy of the asthmatics, lung function improved and the percentages of CD4 T-LC expressing mRNA encoding IL-3, IL-5, and GM-CSF but not IL-2, IL-4, or IFN-gamma were reduced (P < 0.04). Secretion of eosinophil survival-prolonging activity by the CD4 T-LC was also reduced (P = 0.004). We conclude that peripheral blood CD4 but not CD8 T-LC from asthmatics express cytokine mRNA in a Th2-type pattern and show elevated secretion of cytokines prolonging eosinophil survival. Glucocorticoid therapy of asthmatics is associated with a reduction in the percentages of CD4 T-LC expressing IL-3, IL-5, and GM-CSF mRNA and secretion of the corresponding proteins.
 ...
PMID:Peripheral blood CD4 but not CD8 t-lymphocytes in patients with exacerbation of asthma transcribe and translate messenger RNA encoding cytokines which prolong eosinophil survival in the context of a Th2-type pattern: effect of glucocorticoid therapy. 774 19

While LCF is present in BAL early after antigen challenge, we know little about its other potential effects beyond CD4+ T cell, monocyte, and eosinophil chemotaxis and monocyte and CD4+ T cell activation. The work described here focuses on the hypothesis that the secreted protein products of T cells participate in the airway inflammatory process that underlies human asthma, and in particular that LCF could play an early role because of the unusual responsiveness of LCF-producing T to histamine. To date, most studies have addressed the measurement of cytokines derived from CD4+ T cells (e.g., IL-2, IL-3, IL-4, IL-5, and GM-CSF) in the airways of asthmatics, and attempted to correlate the presence of protein or mRNA with the complexion of the inflammatory infiltrate. These studies have been based upon the reports that there are increased numbers of CD4+ T cells in the airways of asthmatics, and that the presence of eosinophils might correlate with the secretion of TH2-type cytokines like IL-3, -4, and -5. Using this information as a background, our work has approached the problem in an entirely different way. We have focused our attention on the early events in antigen-induced asthma that are responsible for CD4+ cell accumulation in the lung, including CD4+ T cells, eosinophils, and monocytes. We have attempted to identify mechanisms by which mast cell mediators, in particular histamine, might play a role in the secretion of chemotactic lymphokines that are selective for CD4+ cells by using CD4 itself as a chemotactic factor receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cytokine binding to CD4+ inflammatory cells: implications for asthma. 795 94

Mycobacterium-specific human helper T-cell clones produce a Th1 pattern of cytokines in vitro: interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), but little or no IL-4 or IL-5. To test the hypothesis that a similar Th1-like pattern of cytokine gene expression occurs in vivo in pulmonary tuberculosis we used in situ hybridization to detect cytokine mRNA expression by bronchoalveolar lavage cells from nine patients with microbiologically confirmed tuberculosis and nine control subjects. Because IFN-gamma may also originate from alveolar macrophages, simultaneous immunocytochemistry and in situ hybridization was applied to determine whether cytokine mRNA was localized to bronchoalveolar macrophages in addition to T-lymphocytes. When samples from patients with tuberculosis and control subjects were compared, there was a significant increase in numbers of IFN-gamma mRNA-positive BAL cells per 1,000 among patients with tuberculosis (p < 0.01). Differences between the two groups in the proportions of cells expressing IL-2, IL-4, or IL-5 mRNA were not significant. Expression of IFN-gamma mRNA by macrophages was detected (median, 14.3% of IFN-gamma mRNA-positive BAL cells). However, the majority of IFN-gamma mRNA expressing BAL cells were T-lymphocytes (median, 80.7%). Activation of Th1-like bronchoalveolar T-lymphocytes, together with production of IFN-gamma by alveolar macrophages, may contribute to the local cellular immune response in pulmonary tuberculosis.
 ...
PMID:Evidence for a Th1-like bronchoalveolar T-cell subset and predominance of interferon-gamma gene activation in pulmonary tuberculosis. 814 65

To study the role of IL-5 in allergic airway hyperreactivity, the time course for the production of cytokines, the infiltration of inflammatory cells and the onset of airway hyperreactivity after three inhalations of antigens were studied in mice. The effect of the soluble alpha-chain of murine recombinant interleukin-5 receptor (sIL-5R alpha) on these phenomena was also examined. Whereas IL-5 and IL-4 were produced in significant amounts, IL-1, IL-2 and gamma-interferon (gamma-IFN) were not detected even after three antigen inhalations. Monocytes and eosinophils but not neutrophils increased significantly after the third antigen exposure. The airway responsiveness to acetylcholine increased after the third aeroantigen-challenge. sIL-5R alpha, administered after each antigen-challenge, suppressed BAL eosinophilia with little effect on airway hyperreactivity.
 ...
PMID:Time course study for antigen-induced airway hyperreactivity and the effect of soluble IL-5 receptor. 820 40

The role of T-cell memory in late-phase allergic lung inflammation is not well defined. To evaluate the role of systemic T-cell memory in allergic late-phase lung inflammation, BALB/c mice were injected intraperitoneally with ovalbumin (OVA) or ragweed (RW) allergens (Test I and Test II groups) or saline (control groups C I and C IV) and then challenged intratracheally with the allergen. Late-phase allergic lung inflammation was defined by: (i) recruitment of eosinophils to airways, (ii) IL-5 mRNA upregulation in BAL fluid cells, and (iii) detection of a Th2 cell cytokine profile in BAL fluids. The number of eosinophils recruited in allergic mice following intratracheal challenge with allergen was at least 300-fold higher P < or = 0.01) in mice with allergen-specific T-memory cells in BAL fluid (Test I and Test II) than in control mice without allergen-specific T-memory cells (C I and C IV). Further, the number of eosinophils recruited in Test I and II correlated with the magnitude of in vitro T-cell memory responses (r = 0.93, P < or = 0.04). Moreover, IL-5 mRNA upregulation in BAL cells and Th2 cytokine production in BAL fluids were observed only in Test I and Test II, and not in any of the control groups. Further, results from pulmonary function tests performed on the same allergic animals indicated that only animals from Test I and Test II groups had impaired lung function after allergen challenge. Taken together, these data strongly suggest that allergen-specific Th2-type T-cell memory is required for the development of allergic asthma. That is, without T-cell memory responses, no eosinophil recruitment and release of EPO (which is known to induce bronchoconstriction) occurred in the airways, and no Th2 cytokine profile was detected in the BAL fluid. Furthermore, if the Th2 cytokine profile was absent, then pulmonary functions remained normal.
 ...
PMID:A role for Th2 T-memory cells in early airway obstruction. 866 Aug 17

We investigated the effects of IL-12 on a murine model of allergic lung inflammation. Administration of IL-12 was timed to interfere with either allergic sensitization (early dosage) or the hypersensitivity inflammatory response in the lung (late dosage), or both (early and late dosages). Comparisons of IL-12- and PBS-treated animals within each treatment group revealed several noticeable effects of IL-12. Early dosage, and the combination of early and late dosages, strikingly decreased ragweed-specific serum IgE, tracheal ring reactivity to acetylcholine, and BAL eosinophilia following allergen challenge. In contrast, late dosage had no effect on IgE levels and only a minimal effect on tracheal ring reactivity, but had a modest effect on recruitment of eosinophils. Early dosage down-regulated IL-5 and IL-10, but did not alter IL-4 or IFN-gamma expression. Late dosage down-regulated IL-5, up-regulated IL-10 and IFN-gamma, but did not change IL-4 expression. The combination of early and late dosage down-regulated IL-4, IL-5, and IL-10 expression, but increased IFN-gamma expression and production in the BAL cells and fluids. Taken together, these results indicate that IL-12 has potent immunomodulatory effects on allergic lung inflammation that depend on the timing of IL-12 administration relative to allergic sensitization and allergen challenge.
 ...
PMID:Immunomodulatory effects of IL-12 on allergic lung inflammation depend on timing of doses. 889 55

Cysteinyl leukotrienes are important mediators of asthma, and inhibition of their effects may represent a potential breakthrough in the therapy of allergic rhinitis and asthma. Strategies for inhibition of cysteinyl leukotriene receptors and inhibition of 5-lipoxygenase activity. The leukotrienes antagonists, with particular reference to asthma and allergic rhinitis, is reviewed in this paper. In studies in asthmatic patients, these compounds can inhibit bronchoconstriction in response to exercise, aspirin and allergen. Results from clinical studies using receptor antagonists, such as LY-171883, SK&F-104353, ICI-204219, ONO-1078, MK-751, MK-0679, demonstrate beneficial effects, with improvement in symptoms and forced expiratory volume in one second (FEV1), and a reduction in the use of beta 2-adrenergic relief medication. NZ-107 was studied for its effect on airway inflammation caused by intratracheal injection of LTB4 or IL-5, or by inhalation of PAF, and by cell activation. Analysis of the BAL fluid revealed that both induced eosinophilia and neutrophilia were suppressed. Surprisingly, although PAF and superoxide generation were inhibited in macrophages and eosinophils, NZ-107 had no effect on neutrophil activation. U-75302 was studied in guinea pigs and inhibited LTB4 induced chemotaxis of eosinophils in vitro and antigen-induced lung eosinophilia in vivo. Further studies are needed to clarify the exact mechanism by which these compounds provide beneficial effects.
 ...
PMID:Leukotrienes and their antagonists in allergic disorders. 915 Aug 42


1 2 3 4 5 6 7 Next >>