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Title: Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

Abstract

Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs. On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did notmore » affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-{alpha} levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later.« less

Authors:
 [1];  [1];  [1];  [2];  [3];  [3];  [1];  [4];  [5]
  1. Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA, Utrecht (Netherlands)
  2. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht (Netherlands)
  3. TNO Nutrition and Food Research Institute, Zeist (Netherlands)
  4. (Netherlands)
  5. Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA, Utrecht (Netherlands). E-mail: p.a.j.henricks@pharm.uu.nl
Publication Date:
OSTI Identifier:
20783426
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 211; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2005.05.012; PII: S0041-008X(05)00298-X; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANHYDRIDES; ASTHMA; DAMAGE; INFLAMMATION; INHALATION; LIPOSOMES; LUNGS; MACROPHAGES; MOLECULAR WEIGHT; OCCUPATIONAL EXPOSURE; RATS

Citation Formats

Valstar, Dingena L., Schijf, Marcel A., Nijkamp, Frans P., Storm, Gert, Arts, Josje H.E., Kuper, C. Frieke, Bloksma, Nanne, Faculty of Biology, Utrecht University, Utrecht, and Henricks, Paul A.J.. Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma. United States: N. p., 2006. Web. doi:10.1016/j.taap.2005.05.012.
Valstar, Dingena L., Schijf, Marcel A., Nijkamp, Frans P., Storm, Gert, Arts, Josje H.E., Kuper, C. Frieke, Bloksma, Nanne, Faculty of Biology, Utrecht University, Utrecht, & Henricks, Paul A.J.. Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma. United States. doi:10.1016/j.taap.2005.05.012.
Valstar, Dingena L., Schijf, Marcel A., Nijkamp, Frans P., Storm, Gert, Arts, Josje H.E., Kuper, C. Frieke, Bloksma, Nanne, Faculty of Biology, Utrecht University, Utrecht, and Henricks, Paul A.J.. Wed . "Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma". United States. doi:10.1016/j.taap.2005.05.012.
@article{osti_20783426,
title = {Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma},
author = {Valstar, Dingena L. and Schijf, Marcel A. and Nijkamp, Frans P. and Storm, Gert and Arts, Josje H.E. and Kuper, C. Frieke and Bloksma, Nanne and Faculty of Biology, Utrecht University, Utrecht and Henricks, Paul A.J.},
abstractNote = {Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs. On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-{alpha} levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later.},
doi = {10.1016/j.taap.2005.05.012},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 211,
place = {United States},
year = {Wed Feb 15 00:00:00 EST 2006},
month = {Wed Feb 15 00:00:00 EST 2006}
}
  • Eighteen workers exposed to trimellitic anhydride (TMA) powder were evaluated in 1979. Twelve of these workers were available for longitudinal study until 1982. Annual clinical evaluations and serum radioimmunoassays for total antibody binding and specific IgE binding to /sup 125/I-TM-HSA were performed. In 1979, five workers had antibody against TM-HSA. Of these, three workers were diagnosed with the late respiratory systemic syndrome (LRSS) and one worker with TMA-induced allergic rhinitis. The LRSS workers had significantly elevated total antibody binding of /sup 125/I-TM-HSA and the worker with rhinitis had significantly elevated specific IgE binding of /sup 125/I-TM-HSA per milliliter of serum.more » Although TMA handling was intermittent throughout the year, average airborne dust concentrations from 1974 to 1978 at job stations of the two heaviest TMA-exposed occupations, operator and assistant operator, were 2.1 and 0.82 mg/m3, respectively. After local exhaust ventilation had been improved, average airborne dust concentrations of TMA at the two latter job stations fell to levels of 0.03 and 0.01 mg/m3, respectively, in 1982. The decrease in TMA exposure coincided with a gradual fall in total antibody binding of /sup 125/I-TM-HSA per milliliter in 1982 and symptomatic improvement in the three individuals with the LRSS. The continuous low-level exposure of the worker with TMA rhinitis was sufficient to elicit a rise in specific IgE against TM-HSA from 1.1 ng of 125I-TM-HSA bound per milliliter in 1979 to 2.12 in 1982.« less
  • The possible modulation of asbestos-related cell death using antioxidants in both target and effector cells of asbestosis was investigated. After exposure to crocidolite asbestos at a range of concentrations (2.5-25 ..mu..gcm/sup 2/ dish), the viability of a normal rat lung fibroblast line and freshly isolated alveolar macrophages (AM) was determined. In comparison to fibroblasts, AM were more resistant to the cytotoxic effects of asbestos. Cytotoxic concentrations of asbestos then were added to both cell types in combination with the antioxidants, superoxide dismutase (SOD), a scavenger of superoxide (O/sub 2//sup -./), and catalase, an enzyme scavenging H/sub 2/O/sub 2/. Dimethylthiourea (DMTU),more » a scavenger of the hydroxyl radical (OH/sup ./) and deferoxamine, an iron chelator, also were evaluated in similar studies. Results showed significant dosage-dependent reduction of asbestos-associated cell death with all agents. In contrast, asbestos-induced toxicity was not ameliorated after addition of chemically inactivated SOD and catalase or bovine serum albumin. Results above suggest asbestos-induced cell damage is mediated by active oxygen species. In this regard, the iron associated with the fiber andor its interaction with cell membranes might be critical in deriving a modified Haber-Weiss (Fenton-type) reaction resulting in production of OH/sup ./.« less
  • The effect of prior ozone (O{sub 3}) exposure on airway hyperresponsiveness and inflammation induced by trimellitic anhydride (TMA) has been investigated in TMA-sensitized guinea pigs. Airway responsiveness was measured as the concentration of acetylcholine needed to increase baseline lung resistance (RL) by 300% (PC300). Ozone (3 ppm, for 3 h) caused an increase in-log PC300 at 1 h after exposure, with return of -log PC300 to control levels at 8 h. Ozone also increased baseline RL at 8 h. TMA challenge increase -log PC300 in TMA-sensitized guinea pigs at 8 h after challenge from 3.85 {+-} 0.09 to 4.11 {+-}more » 0.09. Ozone exposure prior to TMA challenge prevented the induction of airway hyperresponsiveness with a mean -log PC300 of 3.51 {+-} 0.20, which was not different from that of control TMA-Sensitized group. Baseline RL was significantly higher in ozone-pretreated animals after TMA challenge when compared to those of either control or challenged with TMA alone. Ozone had no effect on TMA challenge-induced BAL eosinophilia and neutrophilia. We conclude that a single exposure to ozone inhibits the increase in airway responsiveness, but increases the bronchoconstrictor response induced by TMA in TMA-Sensitized guinea pigs; however, the inflammatory airway response to TMA is unchanged by preexposure to ozone. 29 refs., 2 figs., 1 tab.« less
  • Trimellitic anhydride (TMA) and its precursor trimellitic acid (TMAc) are chemical intermediates widely used in the coatings and plastics industries. The production of an exposure atmosphere necessary for the development of an inhalation animal model to study the effects of TMA and TMAc has been severely hampered because of the highly charged, hygroscopic, and poor packing characteristics of these two chemicals. Several attempts to conduct inhalation exposures using commercially available generators have been unsuccessful, particularly at the extremely low concentrations required (the TLV of TMA is 40 ..mu..g/m/sup 3/). The Model 3400 TSI fluidized bed aerosol generator contained a continuousmore » feed bead-chain system that, with minor modifications, was capable of delivering consistent quantities of powder to the fluidized bed chamber until a buildup of the powder at the nozzles caused the generator to clog, thus failing to produce consistent and reproducible aerosols. The TSI fluidized bed aerosol generator was modified so that its chain delivery system transported the dust to a newly designed aerosolization unit. The new aerosolization unit drew air from an inlet, past the chain carrying the dust, and through an air jet. The concentrated aerosol was diluted in a 0.5 m/sup 3/ mixing chamber and subsequently delivered by air jets to the mixing turrets of the inhalation chambers. Several inhalation studies, with concentrations as low as 10 ..mu..g/m/sup 3/, were conducted successfully on TMA and TMAc with this system.« less
  • Alveolar macrophages (AM) have a natural function in the human body in keeping the lung tissue sterile and in dealing with any foreign material contaminating the airways. AM increase in number when the lungs are exposed to inhaled particles or gases. These investigations have shown that the number of AM changes in relation to the quantity and the type of compounds inhaled, and that this change can be measured by differential counting of the total number of free lung cells, or of AM alone in samples recovered by lung lavage. A method had been developed by which AM are countedmore » in expectorate samples from exposed workers. A primary aluminum reduction plant was chosen, because the kind and degree of chemical pollution of the working atmosphere had already been relatively well investigated.« less