Mast cells mediate complement activation after acid aspiration.
Mast cells mediate complement activation after acid aspiration.
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酸吸入后肥大细胞介导补体激活。
DOI：
10.1097/00024382-200116010-00004
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Hechtman,HB
中科院分区：
文献类型：
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作者：
Kyriakides,C;AustenJr,WG;Wang,Y;Favuzza,J;Kobzik,L;MooreJr,FD;Hechtman,HB
不明,通过观察C3而不是C4基因敲除小鼠免受渗透性水肿的保护，证明了补体途径在酸吸入中的重要作用。利用肥大细胞缺陷小鼠（W/Wv），我们验证了吸酸后肥大细胞介导补体激活的假设。麻醉小鼠置入气管造瘘管，气管内灌注2 mL/kg 0.1 N HCL。4 h后用125l-白蛋白外渗法计算肺血管通透性。检测血清替代补体途径溶血活性，并进行肺免疫组化。W/Wv小鼠的肺通透性比肥大细胞充足（+/+）动物低62%，与使用溶酶抑制剂chyostatin治疗的+/+小鼠相似（降低65%）。用神经肽P的拮抗剂D-PRO2， D-TRP7, 9-Substance P治疗+/+小鼠，损伤减少66%。经凝血抑素或dpdt-sp治疗的w/wv损伤小鼠和+/+动物血清补体溶血活性未受影响，但未治疗的+/+组血清补体溶血活性下降至65%。肺泡C3沉积在未治疗的+/+损伤小鼠中强烈，而在其他组中没有。我们解释这些数据，表明肥大细胞介导补体激活，通过乳糜酶脱粒，在酸吸后。这种肥大细胞的活性可能受到P物质释放的调节。
mdash;: A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 but not C4 genetic knockout mice are protected from permeability edema. Using mast cell-deficient mice (W/Wv), we tested the hypothesis that mast cells mediate complement activation after acid aspiration. Tracheostomy tubes were placed in anesthetized mice and 2 mL/kg 0.1 N HCL was instilled in the trachea. After 4 h, extravasation of 125l-albumin was used to calculate lung vascular permeability. The serum alternative complement pathway hemolytic activity was examined, and lung immunohistochemistry was performed. Lung permeability in W/Wv mice was 62% less than that of mast cell sufficient (+/+) animals and similar to+/+ mice treated with the chymase inhibitor chymostatin (65% decrease). Treatment of+/+ mice with D-PRO2, D-TRP7, 9-Substance P, an antagonist to the neuropeptide substance P, reduced injury by 66%. Serum complement hemolytic activity was intact in injured w/wv mice and+/+ animals treated with chymostatin or dpdt-sp, but was decreased to 65% in the injured untreated+/+ group. Alveolar C3 deposition was intense in injured untreated+/+ mice but absent in the other groups. We interpret these data to indicate that mast cells mediate complement activation, via chymase degranulation, after acid aspiration. This mast cell activity likely is regulated by the release of substance P.