Petit-Bertron Anne-France, Tabary Olivier, Corvol Harriet, Jacquot Jacky, Clément Annick, Cavaillon Jean-Marc, Adib-Conquy Minou
Unit Cytokines & Inflammation, Institut Pasteur, 28 rue Dr Roux, 75015 Paris, France.
Cytokine. 2008 Jan;41(1):54-60. doi: 10.1016/j.cyto.2007.10.012. Epub 2007 Dec 3.
We compared blood neutrophils (PMNs) collected from healthy subjects with PMNs derived from either blood or airways collected from the same cystic fibrosis (CF) patients. When compared to healthy blood PMNs, CF blood PMNs expressed enhanced level of CD64, a marker of neutrophil activation, and lower level of Toll-like receptor-2 (TLR2). CF airway PMNs expressed enhanced level of TLR4. Interleukin-8 (IL-8) production by CF blood PMNs could be enhanced upon addition of lipopolysaccharide or peptidoglycan, and this production was inhibited by recombinant human IL-10. In contrast, CF airway PMNs released spontaneously high level of IL-8 that was neither further enhanced by microbial activators nor inhibited by recombinant human IL-10. The levels of IL-10 receptors were similar in all types of neutrophils. These data further demonstrate that circulating PMNs from CF patients display a distinct pattern of surface markers, including TLRs, as compared to PMNs from healthy donors, and that airways PMNs from CF patients are primed and resistant to anti-inflammatory signals delivered by IL-10.
我们将从健康受试者采集的血液中性粒细胞（PMN）与从相同囊性纤维化（CF）患者的血液或气道中获取的PMN进行了比较。与健康血液PMN相比，CF血液PMN中中性粒细胞活化标志物CD64的表达水平升高，而Toll样受体2（TLR2）的水平降低。CF气道PMN中TLR4的表达水平升高。添加脂多糖或肽聚糖后，CF血液PMN产生白细胞介素-8（IL-8）的能力增强，且这种产生受重组人IL-10抑制。相比之下，CF气道PMN自发释放高水平的IL-8，微生物激活剂既不能进一步增强其释放，重组人IL-10也不能抑制其释放。所有类型的中性粒细胞中IL-10受体水平相似。这些数据进一步证明，与健康供体的PMN相比，CF患者的循环PMN表现出包括TLR在内的独特表面标志物模式，并且CF患者的气道PMN已被激活且对IL-10传递的抗炎信号具有抗性。
