Role of sensory innervation in the rat pulmonary neutrophil recruitment induced by staphylococcal enterotoxins type A and B

Role of sensory innervation in the rat pulmonary neutrophil recruitment induced by staphylococcal enterotoxins type A and B
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DOI:
10.1016/j.ejphar.2009.04.010
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发表时间:
2009-06-24
影响因子:
5
通讯作者:
Antunes, Edson
Antunes, Edson
中科院分区:
医学2区
文献类型:
--
作者:
Desouza, Ivani A.;Camargo, Enilton A.;Antunes, Edson

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大鼠呼吸道暴露于葡萄球菌肠毒素A (SEA)和B (SEB)诱导明显的中性粒细胞内流。由于感觉神经肽在细胞浸润中起着重要作用,在本研究中,我们研究了它在触发SEA和seb诱导的肺中性粒细胞浸润中的作用。雄性Wistar大鼠气管内注射SEA (3 ng/气管)或SEB (250 ng/气管)。各组动物分别接受不同的体内预处理,测定支气管肺泡灌洗液中中性粒细胞计数及P物质和IL-1水平。用SEA和SEB孵育肺泡巨噬细胞和腹膜肥大细胞,测定其IL-1和tnf - α水平。辣椒素预处理可显著降低SEA和seb诱导的支气管肺泡灌洗液中性粒细胞内流,但这种治疗更有效地降低SEA反应。SR140333(速激肽NK(1)受体拮抗剂)和SR48968(速激肽NK(2)受体拮抗剂)可降低sea诱导的中性粒细胞内流,而仅SR140333可抑制seb诱导的反应。赛heptadine(组胺/5-羟雷公胺受体拮抗剂)和md7222 (5-HT(3)受体拮抗剂)减少SEA和seb诱导的中性粒细胞内流。sea暴露大鼠支气管肺泡灌洗液中P物质和IL-1水平显著升高。-她比SEB。此外,SEA(而非SEB)显著释放肥大细胞tnf - α。在SEA和SEB的作用下,肺泡巨噬细胞中tnf - α和IL-1的产生增加。综上所述,感觉神经肽对SEA和seb诱导的肺中性粒细胞募集有显著贡献,但SEA在更大程度上需要气道感觉神经支配,以及肥大细胞和肺泡巨噬细胞产物的参与。(C) 2009 Elsevier B.V.版权所有
Rat airways exposure to Staphylococcal enterotoxin A (SEA) and B (SEB) induces marked neutrophil influx. Since sensory neuropeptides play important roles in cell infiltration, in this study we have investigated its contribution in triggering SEA- and SEB-induced pulmonary neutrophil infiltration. Male Wistar rats were exposed intratracheally with SEA (3 ng/trachea) or SEB (250 ng/trachea). Animals received different in vivo pretreatments, after which the neutrophil counts and levels of substance P and IL-1 in bronchoalveolar lavage fluid were evaluated. Alveolar macrophages and peritoneal mast cells were incubated with SEA and SEB to determine the IL-1 and TNF-alpha levels. Capsaicin pretreatment significantly reduced SEA- and SEB-induced neutrophil influx in bronchoalveolar lavage fluid, but this treatment was more effective to reduce SEA responses. Treatments with SR140333 (tachykinin NK(1) receptor antagonist) and SR48968 (tachykinin NK(2) receptor antagonist) decreased SEA-induced neutrophil influx, whereas SEB-induced responses were inhibited by SR140333 only. Cyproheptadine (histamine/5-hydroxytriptamine receptor antagonist) and MD 7222 (5-HT(3) receptor antagonist) reduced SEA- and SEB-induced neutrophil influx. The substance P and IL-1 levels in bronchoalveolar lavage fluid of SEA-exposed rats were significantly hi.-her than SEB. In addition, SEA (but not SEB) significantly released mast cell TNF-alpha. Increased production of TNF-alpha and IL-1 in alveolar macrophages was observed in response to SEA and SEB. In conclusion, sensory neuropeptides contribute significantly to SEA- and SEB-induced pulmonary neutrophil recruitment, but SEA requires in a higher extent the airways sensory innervation, and participation of mast cells and alveolar macrophage products. (C) 2009 Elsevier B.V. All rights reserved.