Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allergen molecules from Parietaria judaica pollen, a widely distributed allergy inducer in Southern and Western Europe, have been studied using specific monoclonal antibodies (MAbs). MAbs against IgE-binding components were selected in a 4-step radioimmunoassay. Three different MAbs (AC/1.1, AC/7.1 and AC/15.1) were obtained which recognized epitope(s) located on a polypeptide of 10 Kd (Pj10). This polypeptide displayed the highest IgE-binding ability under either native or SDS-denatured conditions, as determined by immunoadsorption and immunodetection after SDS-PAGE, respectively. The Pj10-containing allergen, purified on an AC/1.1 MAb-Sepharose column, was able to inhibit most of the binding of specific IgE to the pollen extract coupled to paper discs in an inhibition radioallergosorbent test (RAST). The affinity-purified allergen exhibited the same immunoelectrophoretic behaviour as the native allergen.
Mol Immunol 1985 Sep
PMID:Isolation of the major IgE-binding protein from Parietaria judaica pollen using monoclonal antibodies. 241 13

Allergen challenge of sensitized Brown-Norway (BN) rats results in increased excretion of cysteinyl-leukotrienes (cLTs) in bile. It is unclear whether this reflects an increased capacity of lung cells to synthesize 5-lipoxygenase products, and, if so, which cells are of primary importance. We have examined the effects of allergen challenge on the capacity of a mixture of isolated lung cells from ovalbumin (OA)-sensitized BN rats to synthesize LTs and other eicosanoids. Cells were isolated by enzymatic digestion of lung tissue before and either 6 or 24 h after challenge of sensitized rats with either OA or saline. A23187-induced synthesis of eicosanoids by these cells was measured using high-pressure liquid chromatography. OA challenge resulted in a significant influx of neutrophils into the lungs and a significant increase in the synthesis of 5-lipoxygenase products, in particular LTB4, by lung cells after 6 h. There was a positive correlation between the percentage of neutrophils in unfractionated lung cells and the amounts of LTB4 produced by these cells. OA challenge had little or no effect on the production of cLTs and the cyclooxygenase product 12-hydroxy-5,8,10-heptadecatrienoic acid. There was a significant increase in the infiltration of eosinophils into the lungs 24 h after OA challenge but no increase in the production of cLTs by lung cells at this time, suggesting that eosinophils from BN rats are unlikely to be the major site for the production of these substances. This was confirmed in experiments with partially purified eosinophils obtained from Sephadex-treated rats. In contrast, cLTs were major products of arachidonic acid metabolism by alveolar macrophages from BN rats. We conclude that allergen challenge results in an increased capacity of lung cells to synthesize 5-lipoxygenase products, in particular LTB4. Macrophages, rather than eosinophils, may be an important site for the synthesis of cLTs in BN rat lungs.
Am J Respir Cell Mol Biol 1995 Oct
PMID:Cellular infiltration and eicosanoid synthesis in brown Norway rat lungs after allergen challenge. 754 78

T helper 2 (Th2)-like cytokines are thought to play a crucial role in the pathogenesis of airway inflammation in atopic asthma, leading to bronchial hyperresponsiveness. To investigate the role of the principal Th2 cytokine interleukin-4 (IL-4) in asthma, we examined the allergen-induced changes in airway morphology and bronchial responsiveness (BR) in an in vivo mouse model. C57BL/6 mice were actively sensitized to ovalbumin (OVA) and exposed daily to aerosolized OVA or saline (SAL) for 7 days. Twenty-four hours after the last allergen exposure, total and differential counts of bronchoalveolar lavage cells revealed a significant increase of eosinophils and lymphocytes in OVA-exposed immunized mice compared with SAL-exposed animals. In IL-4-deficient (IL-4-/-) mice, treated in the same way, there were substantially fewer eosinophils in bronchoalveolar lavage compared with wild-type mice. Allergen exposure of actively sensitized wild-type mice induced a significant increase of BR to carbachol and to serotonin compared with SAL-exposed mice. In contrast, OVA exposure of immunized IL-4-/- mice did not augment BR to serotonin compared with SAL-challenged IL-4-/- mice. In conclusion, these data indicate that repeated allergen exposure in sensitized mice induces airway inflammation and bronchial hyperresponsiveness, and that IL-4 plays a predominant role in the pathogenesis of both phenomena.
Am J Respir Cell Mol Biol 1995 Mar
PMID:Allergen-induced airway inflammation and bronchial responsiveness in wild-type and interleukin-4-deficient mice. 787 90

Airway inflammation is implicated in the pathogenesis of the airway hyperresponsiveness in asthma. An increased production of inflammatory cell progenitors may contribute to asthmatic airway inflammation. Although the number of circulating inflammatory cell progenitors in asthmatic subjects increases after allergen inhalation, no direct evidence exists for increased bone marrow progenitor production. We examined the effect of allergen inhalation on bone marrow progenitor production in seven dogs that develop allergen-induced airway hyperresponsiveness. The effect of inhaled budesonide, a corticosteroid known to be effective in the treatment of asthma, on allergen-induced bone marrow progenitor production and airway hyperresponsiveness was also examined. Allergen inhalation increased airway responsiveness (P < 0.001) and the number of granulocyte-macrophage colony-forming units (CFU) when cultured with dog serum and either recombinant canine stem cell factor (rcSCF) (P < 0.001) or granulocyte colony-stimulating factor (rcG-CSF) (P = 0.035). Budesonide treatment reduced the allergen-induced increases in airway responsiveness (P = 0.005) and abolished the allergen-induced increases in the numbers of CFU cultured with dog serum and either rcSCF (P < 0.001) or rcG-CSF (P = 0.009). These findings provide the first direct evidence that allergen inhalation increases bone marrow progenitor production and suggest that such increases may contribute to the development of airway hyperresponsiveness in asthma. In addition, the effectiveness of inhaled corticosteroids in asthma may result, in part, from their ability to suppress bone marrow production of inflammatory cells.
Am J Respir Cell Mol Biol 1994 Nov
PMID:Allergen-induced changes in bone marrow progenitors and airway responsiveness in dogs and the effect of inhaled budesonide on these parameters. 794 89

Angiotensin-converting enzyme (ACE; EC 3.4.15.1) may participate in respiratory inflammatory diseases by regulating levels of inflammatory peptides such as bradykinin. The presence of ACE in the human nasal mucosa and in nasal secretions was determined by immunohistochemistry, measures of enzyme activity, and immunoblot. ACE activity was significantly more abundant in the membrane-rich fraction than in the soluble cytosolic fraction of nasal mucosal extracts (74.18 +/- 24.50 versus 3.99 +/- 1.83 pmol/min/mg protein, respectively, P < 0.01 by an enkephalin degradation assay; 89.16 +/- 16.17 versus 2.30 +/- 0.89 mU/mg protein, P < 0.01 by colorimetric assessment of Bz-Gly-Gly-Gly degradation). Topical application of histamine stimulated secretion of ACE activity into nasal lavage fluid (2.90 +/- 0.88 versus 1.53 +/- 0.45 U/liter after saline provocation, P < 0.05 by Bz-Gly-Gly-Gly assay). Allergen challenge also induced nasal secretion of ACE. In both histamine and allergen challenges, ACE release correlated closely with that of the vascular proteins IgG and albumin. Methacholine, a stimulant of glandular secretions, failed to augment ACE levels above baseline. ACE-immunoreactive material was localized by the immunogold technique with silver enhancement to the glycocalyx, between epithelial cells, and to interstitial, extracellular sites in the superficial lamina propria, with the highest intensity of staining immediately beneath the basement membrane. Some ACE was detectable in the mucus material of gland and duct lumens but not in gland cells themselves. Endothelial cells and some interstitial mononuclear cells also stained for ACE. ACE was identified by immunoblotting as a 150 kD band on SDS-PAGE.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 Aug
PMID:Angiotensin-converting enzyme in the human nasal mucosa. 804 77

We have previously reported that bone marrow progenitors in dogs, specifically granulocyte-macrophage colony-forming units (GM-CFU), increase developing airway hyperresponsiveness after inhalation of the allergen Ascaris suum. In the present study, we evaluated whether this increased marrow hemopoietic activity can be stimulated by a factor in serum after allergen challenge. Serum samples taken from dogs prior to and 20 min, 2 h, and 24 h after Ascaris or diluent challenge were added to bone marrow cells aspirated prior to challenge, and GM-CFU measured. A second bone marrow aspirate was performed 24 h after challenge. Nonadherent mononuclear bone marrow cells were incubated for 8 days in the presence of the serum and recombinant canine hemopoietic cytokines (stem cell factor, granulocyte colony-stimulating factor, GM colony-stimulating factor). Eight dogs that developed (airway responders) and eight dogs that did not develop (airway nonresponders) allergen-induced airway hyperresponsiveness were studied. Allergen inhalation increased bone marrow GM-CFU in response to all three growth media in vitro for the airway responder (P < 0.05) but not airway nonresponder dogs. The 24-h serum, taken from the airway responder but not the airway nonresponder dogs, produced a similar increase in granulocyte progenitors when added to the bone marrow taken before allergen inhalation (P < 0.05). These findings demonstrate that bone marrow-derived granulocyte progenitors are upregulated by a factor that can be shown to be present in serum 24 h after allergen challenge in dogs that develop allergen-induced airway hyperresponsiveness. Whether in vivo stimulation of bone marrow inflammatory cell production is necessary for the development of allergen-induced airway hyperresponsiveness remains to be proven.
Am J Respir Cell Mol Biol 1996 Sep
PMID:Allergen-induced increase in bone marrow progenitors in airway hyperresponsive dogs: regulation by a serum hemopoietic factor. 892 77

Increased bone marrow granulocyte-macrophage colony forming units (GM-CFU) in dogs developing allergen-induced airway hyperresponsiveness can be accounted for by a factor(s) present in serum following the allergen challenge. The present study evaluated whether in vitro treatment of bone marrow with budesonide or prostaglandin (PG)E2, prevents allergen-induced bone marrow stimulation. Eight dogs were studied after allergen and diluent inhalation challenges. Budesonide (10[-7] M) or PGE2 (10[-6] M) was added to bone marrow aspirated 24 h after challenge. Budesonide or PGE2 was also added to bone marrow aspirated before challenge, to which serum taken 24 h after challenge was subsequently added. Non-adherent mononuclear bone marrow cells were incubated in the presence of the serum and granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte stimulating factor (G-CSF), or stem cell factor (SCF), and the number of GM-CFU counted. Allergen-induced increases in the number of GM-CFU in bone marrow aspirated 24 h after allergen (P < 0.001) were not attenuated by budesonide or PGE2 treatment (P > 0.05). However, GM-CFU increases in bone marrow aspirated before challenge and incubated with post-allergen challenge serum (P < 0.001) were blocked by either budesonide or PGE2 (P < 0.001). These findings demonstrate that budesonide and PGE2 can act directly on the bone marrow, preventing allergen-induced increases in inflammatory cell progenitor production. This suggests that the bone marrow must be considered as a possible site of action for drugs which attenuate allergen-induced asthmatic responses.
Am J Respir Cell Mol Biol 1997 Nov
PMID:The effect of treatment with budesonide or PGE2 in vitro on allergen-induced increases in canine bone marrow progenitors. 937 15

Increases in inflammatory-cell progenitors have been demonstrated in the bone marrow (BM) after inhalation of Ascaris suum in dogs at the time of allergen-induced airway hyperresponsiveness (AHR). The aim of this study was to evaluate the effect of allergen challenge on trafficking of inflammatory cells and their progenitors from the BM to the lung, using a marker of proliferating cells, bromodeoxyuridine (BrdU). BrdU is a thymidine analogue taken up by the DNA of dividing cells, and can be detected with immunohistochemistry (IHC). The development of AHR was assessed through acetylcholine (ACh) airway responsiveness before and after allergen inhalation. Two groups of dogs were matched for the degree of AHR after a screening allergen challenge. On the study day, one group inhaled allergen (n = 8) and one group inhaled diluent (n = 8). All dogs received equal bolus injections of BrdU before and at 5 h after challenge. Blood samples were taken before challenge and at 5 h and 24 h after challenge, and BM aspirate and bronchoalveolar lavage (BAL) samples were taken 24 h after challenge. BrdU-positive cells were detected in cytospin preparations of these samples, using IHC. Allergen inhalation caused AHR (P < 0.05) at 24 h after allergen challenge, and also an increase in BrdU-positive cells in blood, which was 5.7 +/- 0.6% (mean +/- SEM) after allergen challenge and 2.5 +/- 0.7% after diluent (P < 0.005); in BM the increase in BrdU-positive cells was 27.0 +/- 3.4% after allergen challenge and 18.9 +/- 3.2% after diluent (P = 0.1); and in BAL the increase was 3.2 +/- 0.4% after allergen challenge and 0.8 +/- 0.3% after diluent (P < 0.005). There was a significant correlation between the number of BAL neutrophils and the percentage of BrdU-positive BAL cells (r2 = 0.54, P < 0.05). These results demonstrate an allergen-induced increase in proliferating cells, probably in the BM, and indicate that such cells traffic through the circulation into the lungs in response to allergen inhalation.
Am J Respir Cell Mol Biol 1998 Jun
PMID:Allergen challenge increases cell traffic between bone marrow and lung. 961 80

The aim of this study was to investigate production and cellular sources of brain-derived neurotrophic factor (BDNF) production in allergic asthma. For this purpose a mouse model of chronic and severe ovalbumin (OVA)-induced airway inflammation was developed. Allergen-exposed mice developed elevated immunoglobulin E titers; airway inflammation with influx of lymphocytes, monocytes, and eosinophils; and airway hyperresponsiveness. In addition to an influx of inflammatory cells, interleukin (IL)-4 and IL-5 production were enhanced, macrophages showed morphologic signs of activation, and airway epithelium was thickened and displayed a goblet-cell hyperplasia with a marked mucus production. BDNF was detected using in situ hybridization and enzyme-linked immunosorbent assay. Constitutive expression of BDNF messenger RNA (mRNA) was observed in the respiratory epithelium of sensitized and nonsensitized mouse lungs. In addition, BDNF mRNA was detected in airway inflammatory infiltrations and bronchoalveolar lavage fluid (BALF) cells of OVA-sensitized and aerosol-challenged mice. Highest BDNF protein levels were detected in BALF after long-term allergen aerosol exposure. Analysis of BDNF production by isolated lymphocyte subsets revealed T but not B cells as a cellular source of BDNF. In addition, activated alveolar macrophages were identified as BDNF-positive cells. These data indicate that in allergic airway inflammation BDNF production is upregulated and immune cells serve as a source of BDNF.
Am J Respir Cell Mol Biol 1999 Oct
PMID:Cellular sources of enhanced brain-derived neurotrophic factor production in a mouse model of allergic inflammation. 1050 64

Electrospray ionization mass spectrometry was used to quantify phosphatidylcholine (PC) and phosphatidylglycerol (PG) molecular species in bronchoalveolar lavage fluid (BALF) from control and mild asthmatic subjects after local allergen challenge. BALF was obtained from 5 control and 13 asthmatic subjects before and 24 h after segmental allergen and saline challenge. There were no differences in the ratio of total PC to total PG or in the molecular species composition of PC or PG between the asthmatic and control groups under basal conditions. Allergen challenge in asthmatic but not in control volunteers caused a significant increase in the PC-to-PG ratio because of increased concentrations of PC species containing linoleic acid (16:0/18:2 PC, 18:0/18:2 PC, and 18:1/18:2 PC). These molecular species were characteristic of plasma PC analyzed from the same subjects, strongly suggesting that the altered PC composition in BALF in asthmatic subjects after allergen challenge was due to infiltration of plasma lipoprotein, not to catabolism of surfactant phospholipid. Interactions between surfactant and lipoprotein infiltrate may contribute to surfactant dysfunction and potentiate disease severity in asthma.
Am J Physiol Lung Cell Mol Physiol 2000 Feb
PMID:Phospholipid molecular species of bronchoalveolar lavage fluid after local allergen challenge in asthma. 1066 14


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