Effect of lung surfactant collectins on bronchoalveolar macrophage interaction with Blastomyces dermatitidis: inhibition of tumor necrosis factor alpha production by surfactant protein D.
Effect of lung surfactant collectins on bronchoalveolar macrophage interaction with Blastomyces dermatitidis: inhibition of tumor necrosis factor alpha production by surfactant protein D.
复制标题
肺表面活性剂集合素对支气管肺泡巨噬细胞与皮炎芽生菌相互作用的影响：表面活性剂蛋白 D 抑制肿瘤坏死因子 α 的产生。
DOI：
10.1128/iai.00243-06
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Stevens,DavidA
中科院分区：
文献类型：
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作者：
Lekkala,Madhavi;LeVine,AnnMarie;Linke,MichaelJ;Crouch,ErikaC;Linders,Bruce;Brummer,Elmer;Stevens,DavidA
肺泡表面活性剂调节支气管肺泡巨噬细胞 (BAM) 的抗菌功能。关于支气管肺泡灌洗液 (BALF) 中表面活性剂相关蛋白对 BAM 和皮炎芽生菌相互作用的影响知之甚少。我们研究了 B 刺激的 BAM 对 BALF 增强或抑制 TNF-α 产生的影响。皮炎。用B刺激来自CD-1小鼠的BAM。皮炎不含或含有正常 BALF、表面活性剂蛋白 A 缺陷型 (SP-A−/−) 或表面活性剂蛋白 D 缺陷型 (SP-D−/−) BALF，或 SP-A−/− 和 SP-D−/− BALF 的混合物。使用酶联免疫吸附测定法测量培养物上清液中的肿瘤坏死因子α（TNF-α）。 BALF 的蛋白质浓度已标准化。 BAM plusB.皮炎氏菌（BAM-B. dermatitidis）TNF-α的产生被BALF或SP-A−/−BALF抑制≥47%（在290或580μg蛋白质/ml，P<0.05至0.01）；相反，SP-D−/−BALF 并没有显着抑制 TNF-α 的产生。如果 SP-A−/−BALF 与 SP-D−/−BALF 等量混合，则 BAM-B 会产生 TNF-α。皮炎受到抑制(P<0.01)。最后，将纯 SP-D 添加到 SP-D−/−BALF 中可抑制 BAM-B 产生 TNF-α。皮炎(P<0.01)。皮炎与 BALF 一起孵育并清洗，再加上 BAM，刺激的 TNF-α 产量比未清洗时减少 63%B。皮炎(P<0.05)。 SP-D 通过抗 SP-D 抗体在 BALF 处理的未洗涤 B 上检测到。皮炎免疫荧光测定（IFA）。 BALF 被 B 涂层耗尽。皮炎患者失去抑制TNF-α产生的能力(P<0.05)。 1,3-β-葡聚糖是 BAM 产生 TNF-α 的良好刺激剂，并在 B 上检测到。 IFA 皮炎。 β-葡聚糖与 BALF 一起孵育可抑制 BALF 中 SP-D 与 B 的结合。 IFA 证实的皮炎。我们的数据表明 BALF 中的 SP-D 与 B 上的 β-葡聚糖结合。皮炎，阻断 BAM 接触 β-葡聚糖，从而抑制 TNF-α 的产生。因此，尽管 BALF 成分通常介导抗菌活性，B.皮炎可能利用 BALF 成分（例如 SP-D）来减弱宿主的防御反应；这种效应可以减少炎症和组织破坏，但也可能促进疾病。
Alveolar surfactant modulates the antimicrobial function of bronchoalveolar macrophages (BAM). Little is known about the effect of surfactant-associated proteins in bronchoalveolar lavage fluid (BALF) on the interaction of BAM andBlastomyces dermatitidis. We investigated BALF enhancement or inhibition of TNF-α production by BAM stimulated byB. dermatitidis. BAM from CD-1 mice were stimulated withB. dermatitidiswithout or with normal BALF, surfactant protein A-deficient (SP-A−/−) or surfactant protein D-deficient (SP-D−/−) BALF, or a mixture of SP-A−/−and SP-D−/−BALF. An enzyme-linked immunosorbent assay was used to measure tumor necrosis factor alpha (TNF-α) in culture supernatants. BALFs were standardized in protein concentration. BAM plusB. dermatitidis(BAM-B. dermatitidis) TNF-α production was inhibited ≥47% by BALF or SP-A−/−BALF (at 290 or 580 μg of protein/ml,P< 0.05 to 0.01); in contrast, SP-D−/−BALF did not significantly inhibit TNF-α production. If SP-A−/−BALF was mixed in equal amounts with SP-D−/−BALF, TNF-α production by BAM-B. dermatitidiswas inhibited (P< 0.01). Finally, pure SP-D added to SP-D−/−BALF inhibited TNF-α production by BAM-B. dermatitidis(P< 0.01).B. dermatitidisincubated with BALF and washed, plus BAM, stimulated 63% less production of TNF-α than did unwashedB. dermatitidis(P< 0.05). SP-D was detected by anti-SP-D antibody on BALF-treated unwashedB. dermatitidisin an immunofluorescence assay (IFA). The BALF depleted by a coating ofB. dermatitidislost the ability to inhibit TNF-α production (P< 0.05). 1,3-β-Glucan was a good stimulator of BAM for TNF-α production and was detected onB. dermatitidisby IFA. β-Glucan incubated with BALF inhibited the binding of SP-D in BALF toB. dermatitidisas demonstrated by IFA. Our data suggest that SP-D in BALF binds β-glucan onB. dermatitidis, blocking BAM access to β-glucan, thereby inhibiting TNF-α production. Thus, whereas BALF constituents commonly mediate antimicrobial activity,B. dermatitidismay utilize BALF constituents, such as SP-D, to blunt the host defensive reaction; this effect could reduce inflammation and tissue destruction but could also promote disease.