Desouza Ivani A, Camargo Enilton A, Mariano Nadia S, Optiz-Neto João B, Resende Jorge S, Mello Gláucia C, Costa Soraia K P, De Nucci Gilberto, Antunes Edson
Department of Pharmacology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Eur J Pharmacol. 2009 Jun 24;613(1-3):128-34. doi: 10.1016/j.ejphar.2009.04.010. Epub 2009 Apr 16.
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 higher 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.
大鼠气道暴露于葡萄球菌肠毒素A（SEA）和B（SEB）会引起显著的中性粒细胞浸润。由于感觉神经肽在细胞浸润中起重要作用，在本研究中，我们调查了其在触发SEA和SEB诱导的肺部中性粒细胞浸润中的作用。雄性Wistar大鼠经气管内给予SEA（3 ng/气管）或SEB（250 ng/气管）。动物接受不同的体内预处理，之后评估支气管肺泡灌洗液中的中性粒细胞计数以及P物质和IL-1水平。将肺泡巨噬细胞和腹膜肥大细胞与SEA和SEB一起孵育以测定IL-1和TNF-α水平。辣椒素预处理显著降低了SEA和SEB诱导的支气管肺泡灌洗液中的中性粒细胞浸润，但这种处理在降低SEA反应方面更有效。用SR140333（速激肽NK(1)受体拮抗剂）和SR48968（速激肽NK(2)受体拮抗剂）处理可减少SEA诱导的中性粒细胞浸润，而SEB诱导的反应仅被SR140333抑制。赛庚啶（组胺/5-羟色胺受体拮抗剂）和MD 7222（5-HT(3)受体拮抗剂）减少了SEA和SEB诱导的中性粒细胞浸润。暴露于SEA的大鼠支气管肺泡灌洗液中的P物质和IL-1水平显著高于SEB。此外，SEA（而非SEB）显著释放肥大细胞TNF-α。观察到肺泡巨噬细胞中TNF-α和IL-1的产生因SEA和SEB而增加。总之，感觉神经肽对SEA和SEB诱导的肺部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。
