Fasano M B, Cousart S, Neal S, McCall C E
Department of Medicine, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157.
J Clin Invest. 1991 Nov;88(5):1452-9. doi: 10.1172/JCI115454.
Because of the potential importance of interleukin 1 (IL-1) in modulating inflammation and the observations that human blood neutrophils (PMN) express IL-1 receptors (IL-1R) and synthesize IL-1 alpha and IL-1 beta, we studied the IL-1R on blood PMN from a group of patients with the sepsis syndrome. We report a marked enhancement in the sites per cell of IL-1R expressed on sepsis-PMN of 25 consecutively studied patients compared to 20 controls (patient mean = 9,329 +/- 2,212 SE; control mean = 716 +/- 42 SE, respectively). There was no demonstrable difference in the Kd of IL-1R on sepsis-PMN (approximately 1 nM) as determined by saturation curves of 125I-IL-1 alpha binding and the IL-1R on sepsis-PMN had an apparent Mr approximately 68,000, a value like that of normal PMN. Cytofluorographic analysis indicated that the sepsis-PMN phenotype is a single homogeneous population with respect to IL-1R expression. In contrast, expression of the membrane complement receptor CR3 is not increased on sepsis-PMN. Similar increases in expression of IL-1R were not observed in various other inflammatory processes, including acute disseminated inflammation and organ failure not caused by infection, acute infection without organ failure, and immunopathologies such as active systemic lupus erythematosus and rheumatoid arthritis. Enhanced expression of IL-1R was not related simply to the state of myeloid stimulation. Increased expression of IL-1R on normal PMN was induced in vitro by incubating cells with recombinant human granulocyte-macrophage/colony-stimulating factor for 18 h and this response was inhibited by cycloheximide, suggesting the possibility that de novo synthesis of IL-1R might occur in PMN during the sepsis syndrome.
鉴于白细胞介素1（IL-1）在调节炎症方面的潜在重要性，以及有观察表明人类血液中的中性粒细胞（PMN）表达IL-1受体（IL-1R）并合成IL-1α和IL-1β，我们研究了一组脓毒症综合征患者血液PMN上的IL-1R。我们报告，与20名对照组相比，连续研究的25名患者的脓毒症PMN上表达的IL-1R每细胞位点有显著增强（患者平均值分别为9329±2212 SE；对照组平均值为716±42 SE）。通过125I-IL-1α结合饱和曲线测定，脓毒症PMN上IL-1R的解离常数（Kd）没有明显差异（约1 nM），且脓毒症PMN上的IL-1R表观分子量约为68,000，与正常PMN的值相似。细胞荧光分析表明，就IL-1R表达而言，脓毒症PMN表型是单一的同质群体。相比之下，脓毒症PMN上膜补体受体CR3的表达并未增加。在包括急性播散性炎症和非感染性器官衰竭、无器官衰竭的急性感染以及免疫病理状态如活动性系统性红斑狼疮和类风湿关节炎等各种其他炎症过程中，未观察到IL-1R表达有类似增加。IL-1R表达增强并非简单地与髓系刺激状态相关。通过将正常PMN与重组人粒细胞-巨噬细胞/集落刺激因子孵育18小时，可在体外诱导其IL-1R表达增加，且这种反应被放线菌酮抑制，这表明在脓毒症综合征期间PMN中可能会发生IL-1R的从头合成。
