Zuelli Fabiana Maria das Graças Corsi, Cárnio Evelin Capellari, Saia Rafael Simone
Department of General and Specialized Nursing, School of Nursing of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Med Microbiol Immunol. 2014 Jun;203(3):165-76. doi: 10.1007/s00430-014-0328-3. Epub 2014 Feb 1.
Staphylococcus aureus is a Gram-positive bacteria described as an important causative agent of sepsis. The contact between host leukocytes and bacteria activates the innate immune response. Nitric oxide, tumor necrosis factor (TNF)-α and interleukin (IL)-1β play a key role in increasing microbicidal activity and controlling cell influx into infectious focus. Contrarily, IL-10 acts as an anti-inflammatory cytokine and bacterial killing suppressor. Immunoregulatory properties have also been attributed to hormones, including cholecystokinin (CCK). CCK protects cardiovascular function and inhibits the inflammatory response induced by lipopolysaccharide, product derived from Gram-negative bacteria. Nevertheless, the role of CCK during Gram-positive infection remains a literature gap. Our aims were to investigate whether CCK protects rats against bacterial dissemination during sepsis induced by S. aureus. We determined whether CCK modulates local and systemic inflammatory response, as well as the cell migration into the infectious focus and the bactericidal capacity of leukocytes. Our results revealed that proglumide (nonselective CCK receptor antagonist) pretreated rats showed higher bacterial counts in blood and peritoneal lavage fluid (PLF) and reduced TNF-α and IL-10 levels in PLF. Moreover, the dissemination of S. aureus may be related to the failure of neutrophil and macrophage migration into the peritoneal cavity. Also, CCK improved the phagocytic and bactericidal ability of these inflammatory cells. Noteworthy is that the adoptive transfer of CCK-treated neutrophils and macrophages in septic rats improved immune defense, reducing bacterial number in blood and PLF. All together, our study clearly demonstrates an important protective role of CCK against sepsis induced by S. aureus.
金黄色葡萄球菌是一种革兰氏阳性菌，被认为是脓毒症的重要病原体。宿主白细胞与细菌之间的接触会激活先天免疫反应。一氧化氮、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β在增强杀菌活性和控制细胞流入感染灶方面发挥关键作用。相反，IL-10作为一种抗炎细胞因子，具有抑制细菌杀灭的作用。免疫调节特性也归因于包括胆囊收缩素（CCK）在内的激素。CCK可保护心血管功能，并抑制由革兰氏阴性菌衍生的脂多糖诱导的炎症反应。然而，CCK在革兰氏阳性菌感染中的作用在文献中仍存在空白。我们的目的是研究CCK是否能保护大鼠免受金黄色葡萄球菌诱导的脓毒症期间的细菌播散。我们确定CCK是否能调节局部和全身炎症反应，以及细胞向感染灶的迁移和白细胞的杀菌能力。我们的结果显示，经丙谷胺（非选择性CCK受体拮抗剂）预处理的大鼠血液和腹腔灌洗液（PLF）中的细菌计数更高，PLF中的TNF-α和IL-10水平降低。此外，金黄色葡萄球菌的播散可能与中性粒细胞和巨噬细胞向腹腔的迁移失败有关。而且，CCK提高了这些炎症细胞的吞噬和杀菌能力。值得注意的是，将经CCK处理的中性粒细胞和巨噬细胞过继转移至脓毒症大鼠体内可改善免疫防御，减少血液和PLF中的细菌数量。总之，我们的研究清楚地证明了CCK对金黄色葡萄球菌诱导的脓毒症具有重要的保护作用。
