Nakagome Kazuyuki, Shoda Hisakazu, Shirai Tetsu, Nishihara Fuyumi, Soma Tomoyuki, Uchida Yoshitaka, Sakamoto Yoshio, Nagata Makoto
Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.
Allergy Center, Saitama Medical University, Saitama, Japan.
Respirology. 2017 Jul;22(5):913-921. doi: 10.1111/resp.12982. Epub 2017 Jan 31.
Acute eosinophilic pneumonia (AEP) is characterized by a massive pulmonary infiltration of eosinophils. Mechanisms regulating the selective accumulation of eosinophils in AEP have not been fully established. The objective of this study was to evaluate the mechanisms of eosinophil accumulation in alveolar spaces through examination of bronchoalveolar lavage fluid (BALF) from AEP patients (AEP-BALF).
Eosinophils were isolated from the blood of healthy subjects and were placed on a human pulmonary microvascular endothelial cell monolayer cultured on Transwell filters (Coster, Cambridge, MA, USA). A saline control solution or BALF from patients with AEP, sarcoidosis or hypersensitivity pneumonitis was applied to the lower compartment, and the transendothelial migration of the eosinophils was evaluated. The concentrations of cytokines and chemokines in BALF were also measured.
Transmigration of eosinophils across endothelial cells was only induced by the AEP-BALF. This transmigration was blocked by anti-β integrin mAb. The concentrations of eotaxin-2 and monocyte chemotactic protein (MCP)-4, which are CC chemokine receptor (CCR) 3 ligands, were elevated in the AEP-BALF, and anti-CCR3 mAb or anti-MCP-4 mAb inhibited the AEP-BALF-induced transmigration of eosinophils. Furthermore, the concentration of leukotriene (LT) B was increased in the AEP-BALF, and an LTB receptor antagonist partially suppressed the AEP-BALF-induced transmigration of eosinophils.
These findings suggest that CCR3 ligands including eotaxin-2 and MCP-4, and LTB play a role in the accumulation of eosinophils in AEP.
急性嗜酸性粒细胞性肺炎（AEP）的特征是肺部有大量嗜酸性粒细胞浸润。AEP中调节嗜酸性粒细胞选择性聚集的机制尚未完全明确。本研究的目的是通过检测AEP患者的支气管肺泡灌洗液（AEP - BALF）来评估嗜酸性粒细胞在肺泡腔中积聚的机制。
从健康受试者的血液中分离出嗜酸性粒细胞，将其置于接种在Transwell滤器（美国马萨诸塞州剑桥市Coster公司）上培养的人肺微血管内皮细胞单层上。将生理盐水对照溶液或来自AEP、结节病或过敏性肺炎患者的BALF应用于下室，并评估嗜酸性粒细胞的跨内皮迁移。同时还测量了BALF中细胞因子和趋化因子的浓度。
嗜酸性粒细胞跨内皮细胞的迁移仅由AEP - BALF诱导。这种迁移被抗β整合素单克隆抗体阻断。AEP - BALF中CC趋化因子受体（CCR）3配体嗜酸性粒细胞趋化因子-2和单核细胞趋化蛋白（MCP）-4的浓度升高，抗CCR3单克隆抗体或抗MCP - 4单克隆抗体可抑制AEP - BALF诱导的嗜酸性粒细胞迁移。此外，AEP - BALF中白三烯（LT）B的浓度升高，LTB受体拮抗剂可部分抑制AEP - BALF诱导的嗜酸性粒细胞迁移。
这些发现表明，包括嗜酸性粒细胞趋化因子-2和MCP - 4在内的CCR3配体以及LTB在AEP中嗜酸性粒细胞的积聚中起作用。
