Suppression of leukotriene B4 biosynthesis by endogenous adenosine in ligand-activated human neutrophils.
Suppression of leukotriene B4 biosynthesis by endogenous adenosine in ligand-activated human neutrophils.
复制标题
配体激活的人中性粒细胞中内源性腺苷对白三烯 B4 生物合成的抑制。
DOI：
10.1084/jem.186.8.1401
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发表时间：
1997-10-20
影响因子：
15.3
通讯作者：
Borgeat, P
中科院分区：
文献类型：
--
作者：
Krump, E;Picard, S;Mancini, J;Borgeat, P
腺苷（Adenosine，Ado）可抑制人多形核白细胞（PMN）的多种功能反应。本研究探讨了内源性Ado是否调节配体刺激的中性粒细胞中白三烯（LT）B4的生物合成。Ado在悬浮于Hanks缓冲盐溶液（HBSS）或血浆中的PMN中的测量显示核苷的细胞浓度和时间依赖性积累。用Ado脱氨酶去除内源性Ado或用Ado A2 a受体拮抗剂8-（3-氯苯乙烯基）咖啡因阻断其作用，显著增加了HBSS中配体刺激后LTB 4的生物合成。类似地，通过添加Ado脱氨酶，血浆中配体刺激的中性粒细胞（含有重组LTA 4水解酶，允许蛋白质结合的LTA 4转化）的LTB 4合成得到强烈增强。将红细胞添加到血浆中的PMNs悬浮液中模拟了添加Ado脱氨酶和LTA 4水解酶在配体刺激后增强LTB 4生物合成的作用。红细胞对LTB 4生物合成的这种影响被双嘧达莫（Ado转运抑制剂）或卡托普利（LTA 4水解酶抑制剂）阻断。这些结果表明，内源性Ado有效地下调配体刺激的PMN悬浮液中LTB 4的生物合成，指出了一个潜在的重要调节功能的Ado在炎症渗出液。这些结果还揭示了红细胞在上调LTB 4生物合成中的双重作用，即去除内源性Ado和转化由活化的PMN释放的LTA 4。
Adenosine (Ado) has been shown to suppress several functional responses of human polymorphonuclear leukocytes (PMNs). The current study investigated whether endogenous Ado regulates the biosynthesis of leukotriene (LT)B4 in ligand-stimulated PMNs. Measurements of Ado in PMN resuspended in Hanks' buffered salt solution (HBSS) or plasma showed a cell concentration– and time–dependent accumulation of the nucleoside. The removal of endogenous Ado with either Ado deaminase or the blockade of its action by the Ado A2a receptor antagonist, 8-(3-chlorostyryl) caffeine, markedly increased LTB4 biosynthesis upon ligand stimulation in HBSS. Similarly, LTB4 synthesis by ligand-stimulated PMNs in plasma (containing recombinant LTA4 hydrolase to allow the conversion of protein-bound LTA4) was strongly enhanced by addition of Ado deaminase. Addition of red blood cells to suspensions of PMNs in plasma mimicked the effect of adding Ado deaminase and LTA4 hydrolase in enhancing LTB4 biosynthesis upon ligand stimulation. This effect of red blood cells on LTB4 biosynthesis was blocked by dipyridamole, an inhibitor of Ado transport, or captopril, an inhibitor of LTA4 hydrolase. These results demonstrate that endogenous Ado efficiently downregulates ligand-stimulated LTB4 biosynthesis in PMN suspensions, pointing out a potentially important regulatory function of Ado in inflammatory exudates. These results also unveil a dual role for red blood cells in upregulating LTB4 biosynthesis, namely, the removal of endogenous Ado and the conversion of LTA4 released by activated PMNs.