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

The purpose of this study was to investigate whether platelets are activated and release their products in the human lung after antigen challenge. Using subsegmental antigen challenge as a model of asthma, bronchoalveolar lavage fluids from ragweed-allergic asthmatic subjects were assayed for the alpha granule products, platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG), prior to challenge (baseline) and at 5 min and 19 h after challenge with ragweed antigen. Airway segments challenged with normal saline were used as controls. Five minutes after antigen challenge, levels of platelet products in BAL fluid were not elevated from baseline or normal saline control levels. However, 19 h after antigen challenge, a 10-fold increase in platelet products in BAL fluids was found. The mean PF4 levels increased from baseline and saline control values of less than 1.0 to 7.2 ng/ml (p less than 0.05) 19 h after antigen challenge. beta-TG increased from baseline and control levels of less than 1.0 to 6.6 ng/ml (p less than 0.05). Elevations in PF4 and beta-TG were highly correlated with each other (r = 0.98, p less than 0.0001). Levels of platelet products during the 19-h response correlated with albumin, with kinins, with the prostaglandins 6-keto-PGF1 alpha, PGE2, and PGF2 alpha, and with the eosinophil-derived proteins, eosinophil-derived neurotoxin and eosinophil peroxidase. We conclude that platelet activation in the lung is a feature of the late inflammatory response to antigen challenge and that platelets may play an important role in allergic inflammation and asthma.
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PMID:Platelet activation in the lung after antigen challenge in a model of allergic asthma. 153 19

Eosinophils are found in the blood and tissues of patients with allergic diseases such as asthma, allergic rhinitis and also atopic dermatitis. The number of eosinophils in the diseased tissue generally correlates with the expression of clinical symptoms. Originally, the eosinophil was regarded as having an exclusively protective role, for example in host defense against parasites. More recently, the eosinophil is recognized as being a pro-inflammatory cell that can mediate allergic disease. The eosinophil is active in inflammation through the release of granule proteins and the synthesis and release of inflammatory mediators. The important eosinophil granule proteins are major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil derived neurotoxin (EDN) and eosinophil peroxidase (EPO). These proteins have toxic effects on the surrounding tissue. Of additional importance for the allergic inflammatory reactions are membrane-derived mediators such as leukotriene C4 (LTC4), platelet activating factor (PAF) and Charcot-Leyden crystals. These mediators are synthesized and released after eosinophil activation, and act toxic on surrounding cells. Eosinophils are active in asthma, and increased numbers and eosinophil-derived mediator concentrations have been documented in bronchial biopsies, BAL and sputum. In addition, eosinophil granule proteins and inflammatory mediators are found in nasal secretions in allergic rhinitis. In atopic dermatitis one finds activated eosinophils and depositions of eosinophil granule proteins in skin biopsies. Eosinophils are not only active in mediating allergic inflammation, but interact in cellular networks with antigen presenting cells (APC), mast cells, and T lymphocytes. These other cells influence eosinophil maturation, mobilization, tissue localization and activation.
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PMID:[Eosinophilic granulocytes and their significance in allergic diseases]. 153 93

The following studies were conducted to characterize the bron-chodilatory and antiinflammatory activity of the novel, selective phosphodiesterase-IV inhibitor, CP-80,633 (2'S)5-[3-(2'-exobicyclo[2.2.1]heptyloxy-4-methoxy-phenyl]te trahydro- 2(1H)-pyrimidone, a compound in clinical development for atopic disease. In IgG1 passively sensitized guinea pigs, aerosolized ovalbumin challenge increases both pulmonary eosinophil peroxidase levels and airway obstruction. CP-80,633, administered before ovalbumin challenge, significantly attenuated both the increase in tissue eosinophil peroxidase levels (ED50 = 1.4 mg/kg, p.o.) and airway obstruction (ED50 = 0.93 +/- 0.14 mg/kg,p.o.) 10 to 30 times more potently than theophyl-line. Intraarterially administered CP-80,633 also reversed an established bronchoconstriction initiated by continuous infusion of histamine to guinea pigs (ED50 of 8.2 micrograms/kg vs. 5.6 mg/kg for theophylline). The antiinflammatory effect of CP-80,633 was also examined in atopic monkeys challenged with Ascaris suum (Ag) aerosol. CP-80,633 (1 mg/kg, qid, s.c., 1 hr before antigen challenge) significantly reduced antigen-induced increases in bronchoalveolar lavage neutrophils (72.8 +/- 15.8% inhibition) and eosinophils (61.1 +/- 5.7% inhibition) 4 hr postchallenge, but did not reduce leukocytes 24 hr postchallenge. CP-80,633 did not inhibit antigen-induced increases in BAL levels of interleukin-1 beta, -6 or -8 as measured by enzyme-linked immunosorbant assay. These results indicate that CP-80,633 possesses bronchodilatory activity in guinea pigs and some antiinflammatory effects in both guinea pigs and monkeys.
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PMID:The in vivo pharmacology of CP-80, 633, a selective inhibitor of phosphodiesterase 4. 881 22

In the guinea pig, interleukin-5 (IL-5) has been shown to induce airway hyperresponsiveness as well as eosinophilia, which are important symptoms in asthma. IL-5 seems to be a critical cytokine since it selectively affects eosinophil functions. The mechanism of action by which IL-5 leads to airway hyperresponsiveness may be important for our understanding of the pathogenesis of asthma. Neurogenic inflammation, which is mediated by nonadrenergic noncholinergic nerves (NANC), may play a role in the IL-5-induced effects in guinea pig airways. In this study, the role of neuropeptides in the IL-5-induced airway hyperresponsiveness and eosinophilia in the guinea pig was examined using selective neurokinin receptor antagonists. Intra-airway application of IL-5 (1 microgram, twice) induces a selective eosinophil migration (control: 12 [8-22] x 10(5) cells and IL-5: 90 [67-187] x 10(5) cells, p < 0.05) and activation (control: 6.3 +/- 0.9 ng eosinophil peroxidase [EPO]/ml bronchoalveolar lavage [BAL] fluid and IL-5: 29.3 +/- 4.9 ng EPO/ml BAL fluid, p < 0.05) and a pronounced airway hyperresponsiveness in vivo. The maximal responses to histamine are increased by 160 +/- 16% (p < 0.05) after IL-5. Treatment of guinea pigs with either the nonselective neurokinin (NK)-receptor antagonist, FK224, or the selective NK2-receptor antagonist, SR48968, results in a complete inhibition of the in vivo hyperresponsiveness found after application of IL-5. Vice versa, intra-airway administration of substance P (10 micrograms, twice) results in an airway hyperresponsiveness (increased maximal response after substance P: 166 +/- 15% [p < 0.05]) without inducing migration or activation of eosinophils. All examined NK-receptor antagonists do not influence the IL-5-induced eosinophil accumulation. In addition, no effect of the NK-receptor antagonists is observed on the IL-5-induced eosinophil activation, as determined by BAL fluid EPO levels. The release of NK2-receptor active tachykinins plays an important role in the development of IL-5-induced airway hyperresponsiveness. This feature appears to be a step following eosinophil infiltration and activation since there are no effects on eosinophil function by pretreatment of the used NK-receptor antagonists.
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PMID:Role for neurokinin-2 receptor in interleukin-5-induced airway hyperresponsiveness but not eosinophilia in guinea pigs. 927 11

In addition to being an air pollutant, NO2 is a potent inflammatory oxidant generated endogenously by myeloperoxidase and eosinophil peroxidase. In these studies, we sought to determine the effects of NO2 exposure on mice with ongoing allergic airway disease pathology. Mice were sensitized and challenged with the antigen ovalbumin (OVA) to generate airway inflammation and subsequently exposed to 5 or 25 ppm NO2 for 3 days or 5 days followed by a 20-day recovery period. Whereas 5 ppm NO2 elicited no pathological changes, inhalation of 25 ppm NO2 alone induced acute lung injury, which peaked after 3 days and was characterized by increases in protein, LDH, and neutrophils recovered by BAL, as well as lesions within terminal bronchioles. Importantly, 25 ppm NO2 was also sufficient to cause AHR in mice, a cardinal feature of asthma. The inflammatory changes were ameliorated after 5 days of inhalation and completely resolved after 20 days of recovery after the 5-day inhalation. In contrast, in mice immunized and challenged with OVA, inhalation of 25 ppm NO2 caused a marked augmentation of eosinophilic inflammation and terminal bronchiolar lesions, which extended significantly into the alveoli. Moreover, 20 days postcessation of the 5-day 25 ppm NO2 inhalation regimen, eosinophilic and neutrophilic inflammation, pulmonary lesions, and AHR were still present in mice immunized and challenged with OVA. Collectively, these observations suggest an important role for NO2 in airway pathologies associated with asthma, both in modulation of degree and duration of inflammatory response, as well as in induction of AHR.
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PMID:Nitrogen dioxide enhances allergic airway inflammation and hyperresponsiveness in the mouse. 1608 73

Helminths and their products have a profound immunomodulatory effect upon the inductive and effector phases of inflammatory responses, including allergy. We have demonstrated that PAS-1, a protein isolated from Ascaris suum worms, has an inhibitory effect on lung allergic inflammation due to its ability to down-regulate eosinophilic inflammation, Th2 cytokine release and IgE antibody production. Here, we investigated the role of IL-12, IFN-gamma and IL-10 in the PAS-1-induced inhibitory mechanism using a murine model of asthma. Wild type C57BL/6, IL-12(-/-), IFN-gamma(-/-) and IL-10(-/-) mice were immunized with PAS-1 and/or OVA and challenged with the same antigens intranasally. The suppressive effect of PAS-1 was demonstrated on the cellular influx into airways, with reduction of eosinophil number and eosinophil peroxidase activity in OVA+PAS-1-immunized wild type mice. This effect well correlated with a significant reduction in the levels of IL-4, IL-5, IL-13 and eotaxin in BAL fluid. Levels of IgE and IgG1 antibodies were also impaired in serum from these mice. The inhibitory activity of PAS-1 was also observed in IL-12(-/-) mice, but not in IFN-gamma(-/-) and IL-10(-/-) animals. These data show that IFN-gamma and IL-10, but not IL-12, play an important role in the PAS-1 modulatory effect.
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PMID:PAS-1, a protein from Ascaris suum, modulates allergic inflammation via IL-10 and IFN-gamma, but not IL-12. 1900 20