Guinea pig ozone-induced airway hyperreactivity is associated with increased N-acetyl-β-D-glucosaminidase activity in bronchoalveolar lavage fluid

Db, Lew; Chodimella,; Cg, Murlas

doi:10.1007/bf02719704

Cited by 11 publications

(6 citation statements)

References 29 publications

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“…The observed increase in the activities of acid hydrolases is in good agreement with previous reports [ 10,23,24,31]. It has been suggested that bronchoalveolar macrophages, particularly macrophage lysosomes [1 I], release these enzymes, contributing to the destructive effects on tissue.…”

Section: Discussionsupporting

confidence: 81%

Cyclophosphamide induced early biochemical changes in lung lavage fluid and alterations in lavage cell function

Venkatesan

Chandrakasan

1994

Lung

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The present investigation evaluated the changes in bronchoalveolar lavage fluid (BALF) biochemical constituents and indices of bronchoalveolar lavage cell functions to detect early lung injury in rats following intraperitoneal administration of cyclophosphamide (CP). Rats were exposed to a single intraperitoneal injection of CP (200 or 300 mg/kg body weight). Experimental and control rats were sacrificed at various time intervals (2, 3, 5, 7, 11, 21, and 42 days after cessation of exposure), and lung lavage was performed to examine several markers of lung injury. Biochemical analyses revealed dose-related increases in BALF angiotensin converting enzyme activity, total protein, lactate, lactate dehydrogenase, and N-acetyl-beta-D-glucosaminidase (NAG) levels on days 2, 3, 5, 7, and dose-related increases in albumin, alkaline phosphatase, acid phosphatase, and lipid peroxidation on days 2, 3, 5, 7, and 11 after CP treatment. In contrast, reduced levels of ascorbic acid and glutathione (GSH) content were observed in lung lavage fluid. We also examined bronchoalveolar lavage cells for acid hydrolases (acid phosphatase, beta-glucuronidase, NAG) and GSH content. Activity of acid hydrolases was slightly elevated on day 2 and peaked on days 3, 5, and 7. However, lavage cell GSH content was decreased. Thus, measurements of pulmonary changes by analyzing lavage fluid and lavage cell functions seems to be a useful marker for assessing the early onset and development of CP-induced lung injury.

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Section: Discussionsupporting

confidence: 81%

Cyclophosphamide induced early biochemical changes in lung lavage fluid and alterations in lavage cell function

Venkatesan

Chandrakasan

1994

Lung

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“…Treatment of mast cells of endo-α-N-acytelgalactosaminidase, an enzyme that cleaves disaccharides on the cell surface of the mast cell, results in a significant reduction of mast cell adhesion to bronchial epithelium and changes in airway responsiveness 35 . Moreover, a guinea pig model demonstrated increased NAGA released from bronchoalveolar macrophages in animals with increased airways responsiveness following high ozone exposure 36 . Though speculative, given the central role of macrophages and mast cell degranulation in bronchoconstriction, mucus secretion, and airway inflammation in asthmatics 37 , the asthma-associated NAGA eSNP may influence asthma risk through altered glycohydrolase activity.…”

Section: Discussionmentioning

confidence: 97%

A genome-wide survey of CD4+ lymphocyte regulatory genetic variants identifies novel asthma genes

Sharma

Zhou

Thibault

et al. 2014

Journal of Allergy and Clinical Immunology

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Background Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can identify novel asthma genes by enabling prioritization of putative functional variants for association testing. Objective We evaluated 6,706 cis-acting expression-associated variants (eSNP) identified through a genome-wide eQTL survey of CD4+ lymphocytes for association with asthma. Methods eSNP were tested for association with asthma in 359 asthma cases and 846 controls from the Childhood Asthma Management Program, with verification using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by Formaldehyde Assisted Isolation of Regulatory Elements (FAIRE)-qPCR and Chromatin-Immunoprecipitation (ChIP)-PCR in lung derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes. Results Cis-acting eSNP demonstrated associations with asthma in both cohorts. We confirmed the previously-reported association of ORMDL3/GSDMB variants with asthma (combined p=2.9 × 108). Reproducible associations were also observed for eSNP in three additional genes: FADS2 (p=0.002), NAGA (p=0.0002), and F13A1 (p=0.0001). We subsequently demonstrated that FADS2 mRNA is increased in CD4+ lymphocytes in asthmatics, and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity. Conclusions Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes, and provide evidence for the importance of FADS2, NAGA, and F13A1 in the pathogenesis of asthma.

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“…The elevated level ofthe enzyme in lavage fluid was accompanied by a decrease in the intracellular level of the enzyme in alveolar macrophages, thus suggesting that alveolar macrophages are a source ofthe secretion ofthe enzyme into airspace (7). Increased N-acetyl-fl-D-glucosaminidase (EC 3.1.2.30; ,B-hexosaminidase) activity in bronchoalveolar lavage fluid also has been implicated in ozone-induced muscarinic hyperreactivity in the guinea pig model (9). However, the significance of elevated lysosomal hydrolase activity in airways in this animal model and in human subjects is unclear.…”

Section: Introductionmentioning

confidence: 97%

Mitogenic effect of lysosomal hydrolases on bovine tracheal myocytes in culture.

Rattazzi¹

1991

J. Clin. Invest.

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Studies were conducted to assess the mitogenic effect of lysosomal hydrolases, enzymes known to have an association with allergen-or ozone-induced airway hyperreactivity, on bovine tracheal myocytes in culture. Addition of purified human placental jl-hexosaminidase and partially purified bovine liver ,j-glucuronidase resulted in the doubling of cell count after 4 d of incubation in medium M199 with 0.4% FBS. Unstimulated cells remained quiescent without a significant increase of cell count. Lysosomal hydrolases also selectively enhanced 3H-thymidine incorporation four to seven times more than that in vehicle-treated cells or cells treated with endotoxin, a common contaminant of purified enzymes. Ovalbumin (glycoprotein control), pronase, and lysozyme caused a modest but statistically insignificant increase (up to twofold) in 3H-thymidine incorporation. Elastase, collagenase and dialyzed E. colifl-glucuronidase had no effect. The mitogenic effect of hydrolases was equally seen in quiescent, serum-depleted cells as well as in those maintained in medium with 10% FBS, suggesting that it was independent of serum factors. The effect of lysosomal hydrolases was inhibited by exposure to yeast mannan, and mannosylated human serum albumin had a mitogenic effect, suggesting the involvement of a mannose receptor. We conclude that lysosomal hydrolases may play a role in the development of the hyperplasia/hypertrophy of respiratory smooth muscle. (J. Clin. Invest.

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Guinea pig ozone-induced airway hyperreactivity is associated with increased N-acetyl-β-D-glucosaminidase activity in bronchoalveolar lavage fluid

Cited by 11 publications

References 29 publications

Cyclophosphamide induced early biochemical changes in lung lavage fluid and alterations in lavage cell function

Cyclophosphamide induced early biochemical changes in lung lavage fluid and alterations in lavage cell function

A genome-wide survey of CD4+ lymphocyte regulatory genetic variants identifies novel asthma genes

Mitogenic effect of lysosomal hydrolases on bovine tracheal myocytes in culture.

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