Indomethacin and FPL-57231 inhibit antigen-induced airway hyperresponsiveness in sheep

Lanes, Stephan; Stevenson, Jeffrey S.; Codias, Elaine K.; Hernández, Alicia; Sielczak, M. W.; Wanner, Adam; Abraham, William M.

doi:10.1152/jappl.1986.61.3.864

Cited by 60 publications

(18 citation statements)

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“…The sheep develop a natural cutaneous and respiratory reactivity to A. suum. Allergic sheep can be divided into early responders, and dual responders [54]. Dual responders were shown to develop allergen-induced AHR to carbachol at 24 h, whereas sheep with isolated early responses did not [54].…”

Section: Sheepmentioning

confidence: 99%

Animal models of occupational asthma

Mh¹

1994

Eur Respir J

122

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A An ni im ma al l m mo od de el ls s o of f o oc cc cu up pa at ti io on na al l a as st th hm ma a M.H. KarolAnimal models of occupational asthma. M.H. Karol. ERS Journals Ltd 1994. ABSTRACT: Occupational asthma is characterized by variable airflow obstruction occurring in the workplace. The presence of airways inflammation and hyperreactivity provides further evidence for the disease. Since its pathogenic mechanism(s) are unknown, animal models have been developed to investigate the various disease processes, as well as to enable study of environmental and genetic factors which may contribute to disease development.Numerous parameters can be measured in animal systems, including specific and total immunoglobulin E (IgE), pulmonary eosinophilia, diaphragm contractions and airflow muscle hypertrophy. It is recognized that no single factor is sufficient to lead to a conclusion of occupational asthma, but rather that a selected combination of parameters is most fitting. Animal species selected for study have included: mice, rats, guinea-pigs, rabbits, sheep, horses and nonhuman primates. A guinea-pig system has been utilized for more than 90 yrs and has contributed to the basic understanding of physiological and immunological processes involved in allergic respiratory sensitization. The benefits as well as the disadvantages to be derived from each of the animal systems have been enumerated in this review.Certain caveats must be recognized in using animal systems. Attention must always be given to identifying differences which exist between animal and human systems, including morphological, physiological and immunological factors. The extent of bronchus-associated lymphoid tissue (BALT) differs greatly among animal species and probably plays a major role in development of allergic responsiveness in animals. In using animal systems, it must be appreciated that animals are only surrogates. Results from such studies must be compared with information obtained from clinical evaluation in order to avoid faulty extrapolations. Prudent employment of animal models is expected to advance the recognition, treatment and prevention of occupationally-based asthma.

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Section: Sheepmentioning

confidence: 99%

Animal models of occupational asthma

Mh¹

1994

Eur Respir J

122

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“…Whereas the underlying mechanism(s) in the pathogenesis of acute and chronic airway hyperresponsiveness are largely unknown, many recent studies have suggested an active role of nonresident proinflammatory cells that infiltrate specific localities of the lung and which are capable of releasing potent preformed and/or newly generated proinflammatory mediators (2)(3)(4). In particular, an association between blood and lung eosinophilia and bronchial asthma has been firmly established, bronchial hyperresponsiveness has been lacking.…”

Section: Introductionmentioning

confidence: 99%

Human eosinophil major basic protein induces airway constriction and airway hyperresponsiveness in primates.

Gundel

Letts

Gleich³

1991

J. Clin. Invest.

296

149

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We have examined the effects of direct intratracheal instillation of purified eosinophil granule proteins on pulmonary function and airway responsiveness in primates. The results of this study show for the first time that installation of major basic protein (MBP) directly into the trachea of primates results in a significant and dose-related increase in airway responsiveness to inhaled methacholine. Furthermore, MBP and eosinophil peroxidase (EPO) induce a transient bronchoconstriction immediately after instillation that resolves by 1 h postinstillation. In constrast, instillation of other eosinophil granule proteins had no effect on airway responsiveness or pulmonary function. These data indicate a direct role of the eosinophil in the pathogenesis of airway hyperresponsiveness.We suggest that the MBP of human eosinophils has an effector role in the pathogenesis ofairway hyperresponsiveness which may involve active interaction with resident airway tissue cells. MBP may also mediate altered lung function in various inflammatory lung diseases associated with pulmonary eosinophilia. (J. Clin.

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“…In addition, indomethacin, an inhibitor of cyclooxy genase, inhibits the development of airway hyperrespon siveness in allergic sheep [38] and in human subjects [39]. These findings suggest that TX may be involved in the path ogenesis of airway hyperresponsiveness.…”

Section: Discussionmentioning

confidence: 83%

Possible Role of Thromboxane A<sub>2 </sub>in Hyperresponsiveness of Isolated Rat Lung Tissue in a Sephadex-Induced Eosinophilia Model

Takami

Matsumoto²,

Takata³

et al. 1995

Int Arch Allergy Immunol

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Antigen-stimulated contraction and release of chemical mediators were examined in saline- or Sephadex-treated rat lung parenchymal strips. Sephadex treatment caused eosinophilia in the blood and the lung tissue. Antigen challenge of the isolated parenchymal strips in Sephadex-treated rat was followed by passive sensitization, resulted in an augmented contraction and elevated releases of thromboxane (TX) B₂ and peptide-leukotrienes (p-LTs) in bath fluid compared with those of saline-treated control. Although 5-hydroxytryptamine (5-HT) and histamine were significantly released after antigen challenge, the levels were not different between saline- and Sephadex-treated groups. DP-1904, a selective thromboxane synthetase inhibitor, and methysergide but not atropine significantly reduced the augmented contraction and inhibited the elevated TXB₂ release in the Sephadex-treated group. Similar increased contraction and the elevated TXB₂ release above were observed when Sephadex-treated rat lung strips were stimulated by exogenous 5-HT and LTD₄. These augmented contractions were closely correlated with the increase in TXB₂ level (r = 0.83; p < 0.01). In addition, contraction to U-46619, a thromboxane mimetic, was significantly greater in Sephadex-treated rat lung strips. Our results indicate that the ability of Sephadex-treated rat lung tissue to synthesize newly generated mediators such as TXA₂ and p-LTs is increased, and the spasmogenic susceptibility of the lung tissue to TXA₂ itself is modified by Sephadex treatment, suggesting these are due to the augmented contraction in an established hyperresponsiveness state induced by Sephadex.

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Indomethacin and FPL-57231 inhibit antigen-induced airway hyperresponsiveness in sheep

Cited by 60 publications

References 0 publications

Animal models of occupational asthma

Animal models of occupational asthma

Human eosinophil major basic protein induces airway constriction and airway hyperresponsiveness in primates.

Possible Role of Thromboxane A<sub>2 </sub>in Hyperresponsiveness of Isolated Rat Lung Tissue in a Sephadex-Induced Eosinophilia Model

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