Increased elastase and myeloperoxidase activity associated with neutrophil recruitment by IL-17 in airways in vivo
Increased elastase and myeloperoxidase activity associated with neutrophil recruitment by IL-17 in airways in vivo
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DOI：
10.1016/s0091-6749(00)90189-1
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发表时间：
2000-01-01
影响因子：
14.2
通讯作者：
Lindén, A
中科院分区：
文献类型：
--
作者：
Hoshino, H;Laan, M;Lindén, A
工作背景：最近的一项研究表明，气管内给予T淋巴细胞因子IL-17通过C-X-C趋化因子的释放将中性粒细胞募集到体内气道中，目前尚不清楚IL-17是否也可以激活气道中性粒细胞。目的：我们的目的是评估IL-17是否在体内激活气道中的中性粒细胞，如果是的话，促炎细胞因子IL-1 β是否调节IL-17的这种作用。在麻醉的、自主呼吸的大鼠中气管内施用人（h）IL-17或大鼠（r）IL-1 β或hIL-17加rIL-1 β，6小时后进行支气管肺泡灌洗（BAL）。BAL液的特点是中性粒细胞计数，髓过氧化物酶（MPO）的活性，并在某些情况下的弹性蛋白酶（ELA）的活性。分离的大鼠中性粒细胞刺激与hIL-17在体外，随后通过表征MPO活性的细胞medium.Results：hIL-17（1 μ g）增加ELA和MPO活性，以及中性粒细胞计数在BAL液中，而促炎细胞因子rIL-1 β（2.5 ng）没有。rIL-1 β预处理可增强IL-17诱导的ELA和MPO活性，但不增加中性粒细胞计数。BAL ELA活性被中性粒细胞丝氨酸蛋白酶的特异性抑制剂抑制。结论：IL-17在体内可激活中性粒细胞并使其聚集入气道，其作用可能是通过诱导气道其他细胞释放介质而实现的。
Background: A recent study demonstrated that intratracheal administration of the T-lymphocyte cytokine IL-17 recruits neutrophils into airways in vivo by C-X-C chemokine release, It is not known whether IL-17 may also activate airway neutrophils.Objective: Our purpose was to evaluate whether IL-17 activates neutrophils in airways in vivo and, if so, whether the proinflammatory cytokine IL-I beta modulates this action of IL-17.Methods: Intratracheal administration of human (h) IL-17 or rat (r) IL-1 beta or hIL-17 plus rIL-1 beta in anesthetized, spontaneously breathing rats was followed by bronchoalveolar lavage (BAL)6 hours later. The BAL fluid was characterized in terms of neutrophil count, of the activity for myeloperoxidase (MPO), and in some cases of the activity for elastase (ELA). Isolated rat neutrophils were stimulated with hIL-17 in vitro, followed by characterization of MPO activity in the cell medium.Results: hIL-17 (1 mu g) increased the ELA and the MPO activity,as well as the neutrophil count in BAL fluid, whereas the proinflammatory cytokine rIL-1 beta (2.5 ng) did not. Pretreatment with rIL-1 beta enhanced IL-17induced ELA and MPO activity, without increasing the neutrophil count. The BAL ELA activity was inhibited by a specific inhibitor of neutrophil serine proteases. Stimulation with hIL-17 in vitro did not increase MPO activity in isolated neutrophils.Conclusion: IL-17 can activate neutrophils in association with their recruitment into the airways in vivo and this effect is probably achieved through induced release of mediators from other airway cells.