MECHANISTIC STUDIES OF BYSSINOSIS USING AN ANIMAL MODEL

使用动物模型进行全身纤维中毒的机制研究

基本信息

  • 批准号:
    3448663
  • 负责人:
  • 金额:
    $ 5.11万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1984
  • 资助国家:
    美国
  • 起止时间:
    1984-07-01 至 1987-06-30
  • 项目状态:
    已结题

项目摘要

Byssinosis is a respiratory disease seen in cotton textile mill workers. Although characterized clinically for more than a century, both the underlying pathogenesis and etiologic agent(s) remain obscure. This research project is designed to assess pathogenic mechanisms of byssinosis using an animal model. Mechanisms to be evaluated are release of pharmacologic mediators and alterations in the beta-adrenergic system after cotton dust exposure. Experimental evidence suggests both of these may play a role in disease pathogenesis; however, the in vivo challenge studies necessary to confirm these findings are currently lacking. The model will also be used to evaluate lipopolysaccharides (LPS), isolated from the gram-negative bacteria which contaminate cotton dust, as the etiologic agent(s) of byssinosis. An animal model which assesses several mechanisms and correlates these with pulmonary function changes is necessary to discriminate between epi-phenomena and disease-related factors. The advantage of this model is that it closely simulates human dust exposure and disease development. Guinea pigs will be exposed to cotton dust by inhalation for 6 hrs a day, 5 days a week, followed by a two day rest. Exposures will be continued until the animals exhibit a decline in pulmonary function, as measured by whole body plethysmography, when exposed to dust following a two day rest. After this decline in lung function has been demonstrated, animals will be challenged with aqueous cotton dust extract (ACDE), LPS, and, as a control, with microcrystalline cellulose extract (MCE), via intratracheal instillation. Subsequent to in vivo challenge, lungs will be excised and cells teased from tissue. Levels of histamine, thromboxane B2, prostaglandin (PG) F2a, PGE2, and leukotrienes released from this tissue into the supernatant will be determined. The effect on the beta-adrenergic system will be evaluated, in lung cells, by quantitating receptor number and assessing their functional ability by evaluating cyclic AMP production after stimulation with isoproterenol. To assess the role of LPS in the etiology of byssinosis, guinea pigs will be exposed to LPS coupled with an inert carrier (microcrystalline cellulose). After exposures, animals will be challenged with ACDE, LPS, or MCE, as above. Resulting data should determine whether exposure to LPS simulates effects of cotton dust exposure and establish the role of LPS in byssinosis pathogenesis.
棉纤维病是一种常见于棉纺织厂工人的呼吸道疾病。 尽管世纪以来, 潜在的发病机制和病原体仍不清楚。 这 一项研究项目旨在评估棉纤维病的致病机制 使用动物模型。 有待评价的机制是 β-肾上腺素能系统的药理学介质和改变 棉尘暴露。 实验证据表明,这两种可能 在疾病发病机制中发挥作用;然而,体内挑战研究 目前还缺乏必要的证据来证实这些发现。 该模型将 也可用于评价从大肠杆菌中分离的脂多糖(LPS), 污染棉尘的革兰氏阴性细菌, 棉纤维沉着病的病原体。 评估几种机制并将其与 肺功能变化是必要的,以区分 流行现象和疾病相关因素。 这种模式的优点是 它能很好地模拟人类接触粉尘和疾病的发展。 豚鼠将通过吸入暴露于棉尘,每天6小时, 一周两天,然后休息两天。 暴露将持续至 动物表现出肺功能的下降,如通过整体测量的, 身体体积描记法,当暴露于灰尘后休息两天。 后 这种肺功能的下降已经得到证实,动物将 用水性棉尘提取物(ACDE)、LPS攻击,并且,作为对照, 与微晶纤维素提取物(MCE),经皮给药 灌输 体内激发后,将切除肺, 从组织中分离的细胞。 组胺,血栓素B2, 前列腺素(PG)F2a、PGE2和从该组织释放的白三烯 上清中的含量将被确定。 对β-肾上腺素能 将通过定量受体数量在肺细胞中评价系统 并通过评价环磷酸腺苷的产生来评估其功能能力 在用异丙肾上腺素刺激后。 为了评估LPS在棉纤维沉着病病因学中的作用,豚鼠将 暴露于与惰性载体(微晶)偶联的LPS 纤维素)。 暴露后,动物将接受ACDE、LPS或 MCE,如上所述。 所得数据应确定是否暴露于LPS 模拟棉尘暴露的影响,并建立LPS在 棉纤维病发病机制

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Comparison of aqueous grain dusts, cotton dusts, and mold extracts by crossed immunoelectrophoretic techniques.
通过交叉免疫电泳技术比较水性谷物粉尘、棉粉和霉菌提取物。
Use of the cutaneous anaphylactoid test to detect differences in mast cell mediator-releasing activity among LHRH peptides.
使用皮肤过敏测试来检测 LHRH 肽之间肥大细胞介质释放活性的差异。
Antagonistic analogs of luteinizing hormone-releasing hormone are mast cell secretagogues.
黄体生成素释放激素的拮抗类似物是肥大细胞促分泌素。
Fusarium solani: evidence for common antigenic/allergenic determinants with other Fungi Imperfecti.
茄病镰刀菌:与其他不完全真菌共同抗原/过敏决定因素的证据。
  • DOI:
    10.1111/j.1365-2222.1987.tb02330.x
  • 发表时间:
    1987
  • 期刊:
  • 影响因子:
    0
  • 作者:
    O'Neil,CE;Reed,MA;Hughes,JM;Butcher,BT;Lehrer,SB
  • 通讯作者:
    Lehrer,SB
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CAROL ELLIOT O'NEIL其他文献

CAROL ELLIOT O'NEIL的其他文献

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{{ truncateString('CAROL ELLIOT O'NEIL', 18)}}的其他基金

REACTIONS TO TRIMETHOPRIM-SULFAMETHOXAZOLE IN AIDS
艾滋病患者对甲氧苄氨嘧啶-磺胺甲恶唑的反应
  • 批准号:
    3138196
  • 财政年份:
    1988
  • 资助金额:
    $ 5.11万
  • 项目类别:
IMMUNE RESPONSIVENESS IN CHLORINE EXPOSED RATS
氯暴露大鼠的免疫反应
  • 批准号:
    3431154
  • 财政年份:
    1987
  • 资助金额:
    $ 5.11万
  • 项目类别:
IMMUNE RESPONSIVENESS IN CHLORINE EXPOSED RATS
氯暴露大鼠的免疫反应
  • 批准号:
    3431153
  • 财政年份:
    1987
  • 资助金额:
    $ 5.11万
  • 项目类别:
MECHANISTIC STUDIES OF BYSSINOSIS USING AN ANIMAL MODEL
使用动物模型进行全身纤维中毒的机制研究
  • 批准号:
    3448662
  • 财政年份:
    1984
  • 资助金额:
    $ 5.11万
  • 项目类别:

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