5-lipoxygenase products are necessary for ovalbumin-induced airway responsiveness in mice
5-lipoxygenase products are necessary for ovalbumin-induced airway responsiveness in mice
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DOI：
10.1152/ajplung.1997.272.6.l1053
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发表时间：
1997-06-01
影响因子：
4.9
通讯作者：
Funk, CD
中科院分区：
文献类型：
--
作者：
Irvin, CG;Tu, YP;Funk, CD
为了确定5-脂氧合酶产物在抗原暴露后气道反应性发展中的作用，我们通过腹腔注射卵清蛋白和氢氧化铝以及连续暴露于卵清蛋白气溶胶来致敏小鼠。缺乏功能性B-脂氧合酶的小鼠通过靶向基因破坏产生。他们和他们的野生型对照测量肺阻力（R-L）静脉乙酰甲胆碱的反应，支气管肺泡灌洗液细胞计数和血清免疫球蛋白浓度也进行了测量。野生型小鼠的胆碱能反应性显著增加; 5-脂氧合酶缺陷小鼠的乙酰甲胆碱反应性变化最小（最高乙酰甲胆碱剂量时的R-L为9.9 +/- 2.4 cmH（2）O。ml（-1）·s（-1）与对照条件下的27.6 +/- 4.6 cmH（2）O .在野生型小鼠中，加入卵清蛋白后，5.9 +/- 0.9 vs. 7.01 +/- 2.2 cmH（2）O . ml（-1）.s（-1）（5-脂氧合酶缺陷小鼠）。卵清蛋白引起气道嗜酸性粒细胞增多，并增加野生型小鼠的免疫球蛋白，这是目前在5-脂氧合酶缺陷小鼠的程度显着较低。我们的结论是，5-脂氧合酶的产品是必不可少的非特异性气道反应性在小鼠中的生产，并建议，5-脂氧合酶的产品可能是重要的免疫球蛋白的形成。
To determine the role of 5-lipoxygenase products in the development of airway reactivity that follows antigen exposure, we sensitized mice by intraperitoneal injection of ovalbumin and aluminum hydroxide and serial exposure to aerosols of ovalbumin. Mice lacking a functioning B-lipoxygenase enzyme were produced by targeted gene disruption. They and their wild-type controls had measurements of lung resistance (R-L) made in response to intravenous methacholine; bronchoalveolar lavage fluid cell counts and serum immunoglobulin concentrations were also measured. Wildtype mice developed striking increases in cholinergic responsiveness; 5-lipoxygenase-deficient mice manifested minimal alterations in methacholine responsiveness (R-L at the highest methacholine dose was 9.9 +/- 2.4 cmH(2)O . ml(-1).s(-1) under control conditions vs. 27.6 +/- 4.6 cmH(2)O . ml(-1).s(-1) after ovalbumin in wild-type mice; 5.9 +/- 0.9 vs. 7.01 +/- 2.2 cmH(2)O . ml(-1).s(-1) in 5-lipoxygenase-deficient mice). Ovalbumin provoked airway eosinophilia and increased immunoglobulins in wild-type mice, which were present to a significantly lesser degree in 5-lipoxygenase-deficient mice. We conclude that 5-lipoxygenase products are essential for the production of nonspecific airway reactivity in mice and suggest that 5-lipoxygenase products may be important in immunoglobulin formation.