Mast cell mediators prostaglandin-D2 and histamine activate human eosinophils.
Mast cell mediators prostaglandin-D2 and histamine activate human eosinophils.
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DOI：
10.4049/jimmunol.148.11.3536
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发表时间：
1992-06
影响因子：
4.4
通讯作者：
D. Raible;E. Schulman;J. DiMuzio;R. Cardillo;T. Post
中科院分区：
文献类型：
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作者：
D. Raible;E. Schulman;J. DiMuzio;R. Cardillo;T. Post
嗜酸性粒细胞激活引起的继发性呼吸道损伤被认为是哮喘的发病原因之一。用荧光染料Fura-2测定细胞内钙离子浓度，我们发现抗IgE刺激的人肺肥大细胞上清液使人嗜酸性粒细胞胞浆内钙离子增加。然后，我们检测了主要的肥大细胞介质(组胺、PGD2、血小板激活因子(PAF)、过敏嗜酸性粒细胞趋化因子(ECF-A)、白三烯(LT)C4和LTB4)增加嗜酸性粒细胞胞内钙的能力。我们发现PAF(5×10(-9)~5×10(-6)M)和PGD2(1×10(-9)M的五个供体中的两个)对钙动员都有很强的刺激作用。LTB4(10(-8)，10(-7)M)和组胺也是活跃的，尽管需要更高浓度的组胺才能看到反应(3×10(-7)到10(-5)M)。LTC4、Val-ECF-A和ALA-ECF-A处于失活状态。尽管LTB4和PAF增加了中性粒细胞和嗜酸性粒细胞中的钙，但PGD2和组胺对嗜酸性粒细胞的影响是特定的。组胺诱导的细胞内钙升高不能分别被H1或H2拮抗剂吡拉明或西咪替丁(10(-4)M)阻断，但对10(-6)M组胺的反应可被H3拮抗剂硫代巴比妥钠(10(-6)M)完全阻断。为了评估这些刺激性肥大细胞介质对抗IgE刺激的人肺肥大细胞(HLMC)上清液中钙动员活性的相对贡献，我们观察了吲哚美辛和/或5-脂氧合酶途径抑制剂MK886对HLMC上清液中钙动员活性的影响。将这些上清液加入与硫代巴比妥钠和/或PAF拮抗剂WEB-2086预先孵育的Fura-2负载的嗜酸性粒细胞中。我们发现，只有当肥大细胞在吲哚美辛和MK886存在下刺激，并且嗜酸性粒细胞与硫代巴比妥预孵育时，肥大细胞对抗IgE刺激的HLMC上清液反应的嗜酸性粒细胞钙的增加才被完全抑制。WEB-2086效果不明显。当我们检测这些介质对嗜酸性粒细胞分泌功能的影响时，我们发现PGD2(不是组胺)刺激嗜酸性粒细胞增强LTC4的释放，以响应钙离子载体A23187。我们的结论是，PGD2和其他肥大细胞产物对嗜酸性粒细胞的激活可能有助于哮喘特有的呼吸道炎症。
Airway damage secondary to eosinophil activation is thought to contribute to the development of asthma. Using the fluorescent dye FURA-2 to measure the concentration of cytosolic calcium, we found that supernatants from anti-IgE-stimulated human lung mast cells increased cytosolic calcium in human eosinophils. We then examined the major mast cell mediators (histamine, PGD2, platelet-activating factor (PAF), eosinophil chemotactic factor of anaphylaxis (ECF-A), leukotriene (LT)C4 and LTB4) for their ability to increase cytosolic calcium in eosinophils. We found that both PAF (5 x 10(-9) to 5 x 10(-6) M) and PGD2 (two of five donors responsive at 1 x 10(-9) M) were potent stimuli for calcium mobilization. LTB4 (10(-8), 10(-7) M) and histamine were also active, although higher concentrations of histamine were required to see a response (3 x 10(-7) to 10(-5) M). LTC4, val-ECF-A, and ala-ECF-A were inactive. The effects of PGD2 and histamine were specific for eosinophils, although LTB4 and PAF increased calcium in both neutrophils and eosinophils. The histamine-induced increase in intracellular calcium was not blocked by the H1 or H2 antagonists pyrilamine or cimetidine (10(-4) M), respectively; however, the response to 10(-6) M histamine was completely blocked by the specific H3 antagonist thioperamide (10(-6) M). To evaluate the relative contribution of these stimulatory mast cell mediators on the calcium mobilizing activity in supernatants from anti-IgE-stimulated human lung mast cell (HLMC), we examined the effect of supernatants from HLMC pretreated with indomethacin and/or the 5-lipoxygenase pathway inhibitor MK886. These supernatants were added to FURA-2-loaded eosinophils that had been preincubated with thioperamide and/or the PAF antagonist WEB-2086. We found that the increase in eosinophil calcium in response to supernatants from anti-IgE-stimulated-HLMC was totally inhibited only when the mast cells were challenged in the presence of indomethacin and MK886, and the eosinophils were preincubated with thioperamide. WEB-2086 had little effect. When we examined the effect of these mediators on eosinophil secretory function, we found that PGD2 (not histamine) primed eosinophils for enhanced release of LTC4 in response to the calcium ionophore A23187. We conclude that the activation of eosinophils by PGD2 and other mast cell products may contribute to airways inflammation that is characteristic of asthma.