Oxygen radicals contribute to antigen-induced airway hyperresponsiveness in conscious sheep

M. W. Lansing, A. Ahmed, A. Cortes, M. W. Sielczak, Adam Wanner, W. M. Abraham

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

We previously showed that oxygen radicals can induce airway hyperresponsiveness (AHR) in allergic sheep. The purpose of this study was to determine whether antigen challenge results in the generation of free oxygen radicals and if these radicals contribute to antigen-induced AHR. We first determined baseline airway responsiveness in seven Ascaris suum-sensitive sheep by calculating the cumulative provocative concentration of carbachol in breath units (BU; one BU defined as one breath of a 1% wt/vol carbachol solution) that increased specific lung resistance (SRL) 400% over baseline (PC400). On a different day, the sheep underwent inhalation challenge with A. suum antigen, SRL was measured before and immediately after challenge and then hourly for 2 h, at which time SRL had returned to baseline. The postchallenge PC400 was then measured. This procedure was repeated on separate occasions, each at least 14 days apart, except that the sheep were treated with an aerosol of catalase (CAT; 38 mg in 3 ml deionized water), the enzyme that catalyzes the decomposition of hydrogen peroxide (H2O2), at three different times: Trial 1, before antigen and then every 30 min after antigen challenge for 2 h; Trial II, 1 and 2 h after antigen challenge; and Trial III, only at 2 h after antigen challenge. In the control trial, antigen challenge caused a transient (mean ± SEM) 303 ± 48% increase in SRL over baseline (p < 0.05), and 2 h later, PC400 was reduced to 11.0 ± 1.7 BU from a prechallenge value of 24.8 ± 1.9 BU (p < 0.05). None of the treatment regimens affected the immediate response to antigen, but treatments in Trial I (PC400 = 22.3 ± 2.5 BU) and Trial II (PC400 = 23.1 ± 2.5 BU) completely protected against the antigen-induced decrease in PC400. CAT given only at 2 h (Trial III) had no effect on the postantigen PC400 (9.8 ± 1.2 BU). CAT alone given every 30 min for 2 h did not affect PC400. To determine if CAT was affecting inflammatory cell recruitment to the lung, Trial II was repeated in another five sheep. For these experiments the sheep were given CAT or denatured CAT on separate experiment days and bronchoalveolar lavage (BAL) was performed before antigen challenge and after the determination of PC400. Treatment with CAT (1 and 2 h after challenge) again prevented the AHR (pre PC400 = 16.1 ± 3.7 BU, post PC400 = 15.2 ± 2.4 BU), whereas after treatment with denatured CAT PC400 fell to 5.7 ± 1.8 BU from a baseline value of 13.8 ± 2.5 BU (p < 0.05). Despite these differences, inflammatory cells in BAL were not different between the two series of experiments. These results provide indirect evidence that oxygen radicals contribute to antigen-induced AHR. That CAT given only 2 h after challenge failed to block the AHR suggests that H2O2 acted by initiating secondary mechanisms responsible for AHR or that the H2O2 effects were cumulative between 1 and 2 h after antigen.

Original languageEnglish
Pages (from-to)321-326
Number of pages6
JournalAmerican Review of Respiratory Disease
Volume147
Issue number2
StatePublished - Jan 1 1993

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Reactive Oxygen Species
Sheep
Antigens
Ascaris suum
Carbachol
Bronchoalveolar Lavage
Lung
Therapeutics
Aerosols
Catalase
Hydrogen Peroxide
Inhalation
Free Radicals
Water

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Lansing, M. W., Ahmed, A., Cortes, A., Sielczak, M. W., Wanner, A., & Abraham, W. M. (1993). Oxygen radicals contribute to antigen-induced airway hyperresponsiveness in conscious sheep. American Review of Respiratory Disease, 147(2), 321-326.

Oxygen radicals contribute to antigen-induced airway hyperresponsiveness in conscious sheep. / Lansing, M. W.; Ahmed, A.; Cortes, A.; Sielczak, M. W.; Wanner, Adam; Abraham, W. M.

In: American Review of Respiratory Disease, Vol. 147, No. 2, 01.01.1993, p. 321-326.

Research output: Contribution to journalArticle

Lansing, MW, Ahmed, A, Cortes, A, Sielczak, MW, Wanner, A & Abraham, WM 1993, 'Oxygen radicals contribute to antigen-induced airway hyperresponsiveness in conscious sheep', American Review of Respiratory Disease, vol. 147, no. 2, pp. 321-326.
Lansing, M. W. ; Ahmed, A. ; Cortes, A. ; Sielczak, M. W. ; Wanner, Adam ; Abraham, W. M. / Oxygen radicals contribute to antigen-induced airway hyperresponsiveness in conscious sheep. In: American Review of Respiratory Disease. 1993 ; Vol. 147, No. 2. pp. 321-326.
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