Abstract | BACKGROUND: Allergic airway eosinophilia is suppressed by cysteinyl leukotriene (CysLT) receptor ( CysLT1 receptor) antagonists in several species including humans and guinea-pigs, suggesting that CysLTs are directly or indirectly involved in induction of the response. OBJECTIVE: We examined the effect of CysLT antagonists ( pranlukast and MCI-826) on antigen inhalation-induced eosinophilia in peripheral blood and lung, and on IL-5 activity in serum during late increase of airway resistance (late asthmatic response, LAR) in sensitized guinea-pigs. METHODS: Guinea-pigs inhaled ovalbumin (OVA) + Al( OH)3 and OVA mists alternately for sensitization and challenge, respectively, once every 2 weeks. At the fifth challenge, the effects of CysLT antagonists and an anti-IL-5 antibody (TRFK-5) on the occurrence of LAR, and blood and lung eosinophilia, which appeared at 5 h after challenge, were examined. The time-course of IL-5 activity in the serum after the challenge was evaluated by measuring in vitro 'eosinophil survival prolongation activity'. The influence of CysLT antagonists on IL-5 activity was assessed. RESULTS: CysLT antagonists and TRFK-5 completely abolished blood and lung eosinophilia. LAR was suppressed by both MCI-826 and TRFK-5 by 40-50%. Sera obtained from sensitized, challenged animals 3 h and 4 h after challenge induced an obvious prolongation of eosinophil survival. The activity of the sera was completely neutralized by prior exposure to TRFK-5, suggesting that it reflected IL-5 activity. Increased IL-5 activity in the serum was inhibited by both pranlukast and MCI-826 by over 90%. CONCLUSIONS: CysLTs produced after antigen provocation sequentially induced IL-5 production from some immune component cells via CysLT1 receptor activation. Thus, it is likely that CysLTs indirectly cause antigen-induced eosinophilia through IL-5 production.
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Authors | T Nabe, K Yamashita, M Miura, T Kawai, S Kohno |
Journal | Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
(Clin Exp Allergy)
Vol. 32
Issue 4
Pg. 633-40
(Apr 2002)
ISSN: 0954-7894 [Print] England |
PMID | 11972613
(Publication Type: Journal Article)
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Chemical References |
- Chromones
- Interleukin-5
- Leukotriene Antagonists
- Leukotrienes
- Membrane Proteins
- Receptors, Leukotriene
- Thiazoles
- cysteinyl-leukotriene
- MCI 826
- Ovalbumin
- cysteinyl leukotriene receptor 2
- Cysteine
- leukotriene D4 receptor
- pranlukast
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Topics |
- Animals
- Asthma
(immunology)
- Cell Survival
(drug effects)
- Chromones
(pharmacology)
- Cysteine
(physiology)
- Eosinophilia
(blood)
- Guinea Pigs
- Interleukin-5
(antagonists & inhibitors, biosynthesis, physiology)
- Kinetics
- Leukotriene Antagonists
(pharmacology)
- Leukotrienes
(physiology)
- Male
- Membrane Proteins
- Ovalbumin
(immunology)
- Pulmonary Eosinophilia
(immunology)
- Receptors, Leukotriene
- Thiazoles
(pharmacology)
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