ATP acts as an agonist to promote stimulus-induced secretion of IL-1β and IL-18 in human blood
ATP acts as an agonist to promote stimulus-induced secretion of IL-1β and IL-18 in human blood
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DOI：
10.4049/jimmunol.165.8.4615
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发表时间：
2000-10-15
影响因子：
4.4
通讯作者：
Gabel, CA
中科院分区：
文献类型：
--
作者：
Perregaux, DG;McNiff, P;Gabel, CA
LPS刺激培养的单核细胞和巨噬细胞产生大量的proIL-1 β，但向培养基释放的成熟细胞因子很少。用分泌刺激如ATP或尼日利亚菌素处理细胞因子产生细胞，提高原细胞因子转化为其活性的17-kDa物种并释放到细胞外的效率。为了确定这种分泌刺激的需求是否延伸到血液中，个体供者连续4天每天两次放血，收集的血液样本进行两步IL-1生成测定。lps激活的血液样本产生无细胞的IL-1 β，但随后用ATP或尼日利亚菌素处理后，细胞外细胞因子的水平大大增加，三磷酸核苷酸效应的特异性和浓度要求表明P2X(7)受体参与其中。在4天的时间里，单个供体血液在LPS-only和LPS/ATP刺激下产生的IL-1 β的数量相对一致。在供体之间，观察到细胞因子生产能力的一致差异。经ATP处理的血液样本也显示出IL-18生成增强，但tnf - α水平下降。在白细胞中，单核细胞似乎是受ATP刺激影响最大的细胞靶点。这些研究表明，血液需要外源刺激才能有效地产生IL-1 β和IL-18，并表明循环血液单核细胞组成性地表达P2X(7)样受体。
Cultured monocytes and macrophages stimulated with LPS produce large quantities of proIL-1 beta, but release little mature cytokine to the medium. The efficiency at which the procytokine is converted to its active 17-kDa species and released extracellularly is enhanced by treating cytokine-producing cells with a secretion stimulus such as ATP or nigericin, To determine whether this need for a secretion stimulus extends to blood, individual donors were bled twice daily for 4 consecutive days, and the collected blood samples were subjected to a two-step IL-1 production assay. LPS-activated blood samples generated cell-free IL-1 beta, but levels of the extracellular cytokine were greatly increased by subsequent treatment with ATP or nigericin, Specificity and concentration requirements of the nucleotide triphosphate effect suggests a P2X(7) receptor involvement. Quantities of IL-1 beta generated by an individual donor's blood in response to the LPS-only and LPS/ATP stimuli were relatively consistent over the 4-day period, Between donors, consistent differences in cytokine production capacity were observed. Blood samples treated with ATP also demonstrated enhanced IL-18 production, but TNF-alpha levels decreased. Among leukocytes, monocytes appeared to be the most affected cellular targets of the ATP stimulus. These studies indicate that an exogenous stimulus is required by blood for the efficient production of IL-1 beta and IL-18, and suggest that circulating blood monocytes constitutively express a P2X(7)-like receptor.