Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conditions for measuring selectively eosinophil peroxidase (EPO) and the neutrophil myeloperoxidase (MPO) in inflamed rat lung were determined. EPO could be specifically measured with o-phenylene diamine as chromogen at pH 8.0 in the presence of 3 mM bromide and MPO with tetramethylbenzidine as chromogen at pH 5.0 in the absence of bromide but with the EPO inhibitor, resorcinol. Aeroallergen challenge of sensitized Brown Norway rats with ovalbumin, but not with saline, resulted in a pronounced eosinophilic lung inflammation with some focal hemorrhages and an increase in lung wet weights. Quantitation of the eosinophil and neutrophil accumulation required lyophilization of lung samples, a hypotonic wash to remove contaminating hemoglobin, which interfered with the MPO assay, followed by extraction with the detergent cetyltrimethylammonium chloride. Based on lung EPO and MPO activities and standardization of enzyme activity with purified eosinophils and neutrophils, the total number of eosinophils and neutrophils in the lungs was calculated at 24 h (n = 19), 48 h (n = 9) and 72 h (n = 4) after challenge, as 56 +/- 6.4 x 10(6), 119 +/- 28 x 10(6) and 108 +/- 33 x 10(6) for eosinophils, respectively, and 94 +/- 6.8 x 10(6), 49 +/- 5.0 x 10(6) and 32 +/- 5.5 x 10(6) for neutrophils, respectively. We conclude that, with the assay conditions outlined here, EPO and MPO can be used to quantitate the tissue infiltration of eosinophils and neutrophils in the rat even in mixed inflammatory reactions.
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PMID:Quantitation of eosinophil and neutrophil infiltration into rat lung by specific assays for eosinophil peroxidase and myeloperoxidase. Application in a Brown Norway rat model of allergic pulmonary inflammation. 891 92

Epidemiological studies have demonstrated an association between use of carbamate insecticides, including carbaryl, and increased incidence of allergic asthma in farmers. In this study the effect of oral carbaryl exposure on the development of allergic responses to house dust mite (HDM) was examined in female Brown Norway rats. Rats were gavaged for 2 weeks with 0, 2, 10, or 50 mg/kg/day of carbaryl. They were sensitized with a subcutaneous injection of HDM in aluminum hydroxide adjuvant 3 days after the beginning of carbaryl exposure and challenged with antigen via the trachea 1 day after the final carbaryl ingestion. Two days after challenge, antigen-specific cell proliferation in pulmonary lymph nodes was significantly higher in the 50 mg/kg group than in controls, while antigen-specific splenocyte proliferation was decreased in groups dosed with 2, 10, and 50 mg/kg carbaryl. Total protein and lymphocyte number in bronchoalveolar lavage (BAL) fluid were also increased in the 50 mg/kg group. By 7 days after challenge, immune-mediated pulmonary inflammation (eosinophils), antigen-specific immunoglobulin (Ig) E level in serum, and antigen-specific IgE and IgA levels in BAL fluid were significantly elevated in the 50 mg/kg group. No apparent change was observed for lactate dehydrogenase and eosinophil peroxidase in BAL fluid, while the number of BAL macrophages were decreased in groups dosed with 10 and 50 mg/kg carbaryl. The results suggest that carbaryl may cause systemic immune suppression, while enhancing pulmonary allergic responses to house dust mite antigen.
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PMID:Enhanced allergic responses to house dust mite by oral exposure to carbaryl in rats. 972 Jan 42

1. The ability of various C-C chemokines to elicit tissue eosinophil infiltration following intradermal injection or peripheral blood eosinophilia following intravenous injection were compared in the Brown-Norway rat. 2. Eotaxin (0.1 - 3 microg site-1) of human and murine origin produced equivalent, dose-dependent increases in eosinophil peroxidase activity in rat dermis 4 h post-injection. 3. Human eotaxin-2 was equipotent with human eotaxin in terms of dermal eosinophil recruitment. Other human CCR3 agonists, such as MCP-3, RANTES and MCP-4 failed to increase dermal eosinophil peroxidase activity at doses up to 1 microg site-1 whereas the latter did produce a small effect at 3 microg site-1. 4. Consistent with observations in vivo, human eotaxin displaced [125I]-eotaxin from rat spleen membranes more potently (IC50=2 nM) than did MCP-4 (IC50=500 nM). RANTES did not compete with the radiolabelled chemokine at concentrations up to 1 microM. 5. Human eotaxin (5 microg) administered intravenously increased circulating eosinophils approximately 3 fold whereas MCP-4 (5 microg i.v.) increased circulating monocytes approximately 3 fold without affecting eosinophil numbers. 6. Dexamethasone pretreatment inhibited eotaxin-induced dermal eosinophil influx only at a steroid dose (0.1 mg kg-1, s.c.) which significantly reduced circulating eosinophil numbers. The steroid also reduced eosinophilia in peripheral blood resulting from systemic eotaxin administration (5 microg, i.v.). 7. These data suggest differences in rat CCR3 relative to other species as surmised from a distinctive rank order of chemokine potency. In addition to its chemotactic effects eotaxin, but not MCP-4, promotes eosinophil recruitment into the circulation. One of the mechanisms by which glucocorticoids, such as dexamethasone, acutely inhibits eotaxin-induced dermal eosinophil influx is to diminish the circulating numbers of these cells available for tissue recruitment.
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PMID:Characterization of chemokine CCR3 agonist-mediated eosinophil recruitment in the Brown-Norway rat. 1051 63

Epidemiological studies have demonstrated an association between elevated levels of particulate matter (PM) air pollutants and exacerbation of asthma symptoms. We have shown in a Brown Norway (BN) rat model of house dust mite (HDM) allergy that preexposure to residual oil fly ash (ROFA) particles enhanced the sensitization phase such that the secondary immune response and associated lung injury were increased after allergen challenge. To determine whether the metals present in ROFA mediated this effect, BN rats were intratracheally instilled with either ROFA (1000 microg) or acidified saline + NiSO(4) (105.12 microg), VSO(4) (98.2 microg), FeSO(4) (58.49 microg), or a mixture (Mix) of each metal. HDM-specific IgE was higher in the serum of the ROFA, Ni, V, and Mix groups than in the HDM group after challenge, and antigen-induced bronchoconstriction responses were increased in the Ni group. Lymphocyte proliferation to antigen was increased in the ROFA, Ni, and V groups compared to controls. Total protein and eosinophil peroxidase levels were elevated in the Fe group, and eosinophil numbers in the bronchoalveolar lavage fluid (BALF) were increased in the ROFA and Fe groups compared to HDM control. IL-5 and IL-13 mRNA expression was also increased in the lung tissue of all metal and ROFA-treated groups, while BALF IL-10 was elevated in the Fe and Mix groups, and IL-6 and TNF-alpha were elevated in the metal and ROFA-treated groups compared to controls. These results suggest that ROFA's metallic constituents mediate enhancement of sensitization to HDM and that pulmonary inflammation may play a role in this adjuvant effect.
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PMID:Enhanced allergic sensitization by residual oil fly ash particles is mediated by soluble metal constituents. 1081 56

The course of pulmonary edema formation after an intratracheal (i.t.) instillation of ovalbumin was followed noninvasively by magnetic resonance imaging (MRI) in actively sensitized Brown Norway (BN) rats. Changes in edema volume assessed by MRI mimicked the results from the analysis of the number and activation of inflammatory cells recovered from the broncho-alveolar lavage (BAL) fluid. Rats treated with budesonide did not develop edema following challenge with ovalbumin, and these animals showed a significant decrease in BAL fluid inflammatory cell numbers and eosinophil peroxidase and myeloperoxidase activities. Thus, following lung edema formation by MRI provides a reliable means of assessing pulmonary inflammation after allergen challenge. Unlike BAL fluid analysis, which requires killing animals at each time point, this method is noninvasive. MRI could be of importance for the noninvasive profiling of anti-inflammatory drugs in animal models of asthma and in the clinic. Magn Reson Med 45:88-95, 2001.
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PMID:Pulmonary edema induced by allergen challenge in the rat: noninvasive assessment by magnetic resonance imaging. 1114 90

We have investigated the effect of wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase, on the immediate-type allergic response and the late phase pulmonary inflammation induced by allergen challenge in the ovalbumin-sensitised Brown Norway rat. Intratracheal (i.t.) instillation of ovalbumin induced dose-related bronchoconstrictor responses. Administration of wortmannin (1, 10 or 100 microg kg(-1) i.t., 1 h prior to challenge) induced a marked and dose-dependent inhibition of ovalbumin-induced bronchospasm (ED(50) ca. 5 microg kg(-1) i.t.). At similar doses, wortmannin also suppressed the bronchoconstrictor responses to 5-hydroxytryptamine and methacholine but the degree of blockade of these spasmogens (1.4-1.9-fold) was less than that of ovalbumin (>20-fold). Wortmannin, given intratracheally 1 h prior to allergen challenge, also suppressed the increases in bronchoalveolar lavage fluid leukocyte numbers and eosinophil peroxidase activity measured 24 h post challenge. However, relatively high doses were necessary (ED(50) ca. 100 microg kg(-1) i.t.). The potency of wortmannin was increased when dosed 1 h prior to and 24 h after allergen challenge and the readout was 48 h after challenge (ED(50) 3-5 microg kg(-1) i.t.). Thus, wortmannin is a potent inhibitor of the bronchoconstrictor response induced by allergen in the airways of actively sensitised Brown Norway rats. Inhibition of phosphatidylinositol-3-kinase, an obligatory step in mast cell activation in response to allergen, is the presumed mechanism of action. The fact that similar doses of wortmannin do not suppress the late response to allergen suggests a minimal role for the mast cell in generating the late response to allergen in this model. The striking increase in potency to inhibit the late response when dosed 1 h prior to and 24 h after allergen challenge with the readout taken at 48 h may represent an effect of wortmannin to suppress the migration of leukocytes.
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PMID:Effects of wortmannin on airways inflammation induced by allergen in actively sensitised Brown Norway rats. 1175 55

We have investigated the effect of 2(4-((2-carboxymethyl)phenyl)ethylamino)-5'-N-ethylcarboxamidoadenosine (CGS 21680), a potent and selective agonist at adenosine A2A receptors, on pulmonary inflammation induced by allergen challenge in the ovalbumin-sensitised, Brown Norway rat. Aerosol administration of ovalbumin (5 mg x ml(-1) for 60 min; calculated dose 0.4 mg x kg(-1)) induced increases in bronchoalveolar lavage fluid leukocyte numbers, protein content and myeloperoxidase and eosinophil peroxidase activities measured 24 h post challenge. CGS 21680 (10 and 100 microg x kg(-1) given intratracheally (i.t.) 30 min before and 3 h after allergen challenge) inhibited dose-dependently all the parameters of inflammation. Qualitatively similar results were obtained with the glucocorticosteroid, budesonide (0.1, 1 and 10 mg x kg(-1) given 3 h prior to ovalbumin challenge). CGS 21680 given i.t. reduced blood pressure in anaesthetised rats at similar doses to those at which anti-inflammatory effects were manifested. Both the anti-inflammatory and hypotensive responses to CGS 21680 were blocked by pretreatment with the selective adenosine A2A receptor antagonist, 4-(2-(7-amino-2-(2-furyl)(1,2,4)triazolo(2,3-a(1,3,5)triazin-5-yl amino)ethyl)phenol (ZM 241385), 3 mg x kg(-1) p.o., 1 h prior to the agonist. Thus, CGS 21680 manifests broad-spectrum anti-inflammatory activity in a model of allergic asthma in the Brown Norway rat through activation of adenosine A2A receptors. The striking similarity to budesonide, a clinically used anti-inflammatory agent, suggests that adenosine A2A receptor agonists may be useful alternatives to glucocorticosteroids in the treatment of asthma.
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PMID:Effects of CGS 21680, a selective adenosine A2A receptor agonist, on allergic airways inflammation in the rat. 1190 10

A rat bioassay has been developed to provide an objective approach for the identification and classification of respiratory allergy using trimellitic anhydride (TMA), which is a known respiratory tract irritant and asthmagen. Particular emphasis was placed on the study of route-of-induction-dependent effects and their progression upon inhalation challenge with TMA (approximately 23 mg m(-3) for a duration of 30 min), which included analysis of specific and non-specific airway hyperreactivity and pulmonary inflammation initiated and sustained by immunological processes. Refinement of the bioassay focused on procedures to probe changes occurring upon challenge with TMA or methacholine aerosols using physiological, biochemical and immunological procedures. Following challenge with TMA, the rats sensitized to TMA showed marked changes in peak inspiratory and expiratory air flows and respiratory minute volume. In these animals, a sustained pulmonary inflammation occurred, characterized by specific endpoints determined in bronchoalveolar lavage (lactate dehydrogenase, protein, nitrite, eosinophil peroxidase, myeloperoxidase). When compared with the naive controls, lung weights were increased significantly, as were the weights of lung-associated lymph nodes following inhalation induction and auricular lymph nodes following topical induction. The extent of changes observed was equal or more pronounced in animals sensitized epicutaneously (day 0:150 microl vehicle/50% TMA on each flank, day 7; booster administration to the skin of the dorsum of both ears using half the concentration and volume used on day 0) when compared with rats sensitized by 5 x 3 h day(-1) inhalation exposures (low dose: 25 mg TMA m(-3), high dose: 120 mg TMA m(-3)). In summary, the findings support the conclusion that the Brown Norway rat model is suitable for identifying TMA as an agent that causes both an immediate-type change of breathing patterns and a delayed-type sustained pulmonary inflammatory response. However, it remains unresolved whether the marked effects observed in the topically sensitized rats are more related to a route-of-induction or dose-dependent phenomenon.
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PMID:Respiratory hypersensitivity to trimellitic anhydride in Brown Norway rats: a comparison of endpoints. 1192 Sep 32

We have explored the effects of bacterial endotoxin (lipopolysaccharide; LPS) on the response of the airways of Brown Norway (BN) rats to adenosine. Comparisons have been drawn with the effects on responses to methacholine and 5-hydroxytryptamine. In vehicle-challenged animals, adenosine, given i.v. was only a weak bronchoconstrictor. In contrast, 1 h following intratracheal administration of LPS, 0.3 mg kg-1, bronchoconstrictor responses to adenosine were markedly and selectively enhanced. At this time point, there were no significant changes in leukocyte numbers, eosinophil peroxidase and myeloperoxidase activities or protein concentrations in bronchoalveolar lavage (BAL) fluid. Twenty-four hours after challenge, the sensitivity of the airways to both adenosine and methacholine was reduced relative to the earlier time point and there were substantial increases in each marker of inflammation in BAL fluid. The bronchoconstrictor response to adenosine was blocked selectively by methysergide, disodium cromoglycate and the broad-spectrum adenosine receptor antagonist, 8-SPT, but not by DPCPX or ZM 243185, selective antagonists for the A1 and A2A receptors, respectively. Thus, the response to adenosine augmented following LPS is mast cell mediated and involves a receptor which can be blocked by 8-SPT but not by selective A1 or A2A receptor antagonists. It thus bears similarity to the augmented response to adenosine induced by allergen challenge in actively sensitized BN rats. Exposure to LPS could be a factor along with allergen in determining the increased sensitivity of the airways of asthmatics to adenosine.
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PMID:Airway hyperresponsiveness to adenosine induced by lipopolysaccharide in Brown Norway rats. 1197 75

We have recently demonstrated a marked and selective augmentation of the bronchoconstrictor response to adenosine in actively sensitised Brown Norway (BN) rats challenged with ovalbumin (OA). The augmented response is mediated by 5-hydroxytryptamine (5-HT) released as a consequence of mast cell activation. We describe here the effects of budesonide, a clinically used glucocorticosteroid, IMM125, a hydroxyethyl derivative of D-serine-cyclosporine, MLD987, a close analogue of ascomycin and SAR943, a rapamycin derivative, on the hyperresponsiveness to adenosine induced in actively sensitised BN rats by exposure to allergen. Bronchoconstrictor responses to adenosine elicited 3 h following intratracheal (i.t.) instillation of OA, 0.3 mg kg(-1) were reduced dose-dependently by budesonide, IMM125, and MLD987, given i.t. 25 and 1 h prior to allergen challenge. In contrast, SAR943 had no effect on responses to adenosine. Responses to methacholine and 5-HT were minimally affected by these agents. Bronchoconstrictor responses to bradykinin were dose-dependently reduced by budesonide, but unaffected following IMM125, MLD987 or SAR943 pre-treatment. Challenge with OA at a dose of 0.3 mg kg(-1), induced increases in bronchoalveolar lavage (BAL) fluid, leukocyte numbers, eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activities and protein concentration measured 24 h post challenge. Budesonide (1 mg kg(-1) given i.t. 25 and 1 h prior to OA challenge) induced reductions in the BAL fluid parameters of inflammation; IMM125 and MLD987, at a dose of 1 mg kg(-1) had no significant effect whereas SAR943 reduced lymphocyte numbers. Thus, budesonide, IMM125 and MLD987 block the hyperresponsiveness to adenosine induced by allergen challenge in sensitised rats. In the case of budesonide the effect is associated with a powerful, generalised anti-inflammatory effect although an effect directly on the mast cells is also likely. With IMM125 and MLD987, the effect is seen at doses that are not anti-inflammatory and may reflect direct suppression of mast cell activation by these agents.
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PMID:Effects of immunomodulators on airways hyperresponsiveness to adenosine induced in actively sensitised Brown Norway rats by exposure to allergen. 1282 16


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