Increased levels of cyclic adenosine-3',5'-monophosphate in human polymorphonuclear leukocytes after surface stimulation.
Increased levels of cyclic adenosine-3',5'-monophosphate in human polymorphonuclear leukocytes after surface stimulation.
复制标题
表面刺激后人多形核白细胞中环腺苷-3,5-单磷酸水平增加。
DOI：
10.1172/jci109760
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
G. Weissmann
中科院分区：
文献类型：
--
作者：
J. Smolen;H. Korchak;G. Weissmann
人多形核白细胞(PMN)悬液中cAMP(CAMP)(但不包括cAMP)水平在细胞暴露于趋化肽N-甲酰甲硫基亮氨酰苯丙氨酸、免疫复合体牛血清白蛋白/抗牛血清白蛋白和钙离子载体A23187等刺激后迅速增加。刺激后cAMP迅速升高，最高达基础水平的两倍，10-45 S，刺激2-5分钟后，cAMP降至基础水平。CAMP水平的升高与膜超极化(通过摄取亲脂性阳离子三苯甲基膦来测量)同步或跟随，并且总是先于溶酶体酶的释放和超氧阴离子(O2)的产生。通过去除细胞外二价阳离子，用K+或胆碱+取代细胞外Na+，以及使用低浓度的刺激，升高的cAMP水平可以从这些后续事件中解脱出来；这些条件中的每一种实际上都取消了溶酶体酶的释放和O2的产生，同时保持了cAMP水平的刺激升高不受影响。钙离子载体A23187不会引起膜超极化，从而使膜电位的变化与cAMP水平的变化分离。这些数据表明，cAMP在刺激-分泌耦合的最早步骤中不是关键成分。经前列腺素E1或I2处理的细胞表面刺激产生非常高水平的cAMP；这些高水平可能是稳定的前列腺素抑制溶酶体酶释放和O2产生的重要机制的一个重要部分。
Levels of cyclic AMP (cAMP) (but not cyclic GMP) in suspensions of human polymorphonuclear leukocytes (PMN) increased promptly after exposure of the cells to stimuli such as the chemotactic peptide N-formyl methionyl leucyl phenylalanine, the immune complex bovine serum albumin/anti-bovine serum albumin and calcium ionophore A23187. cAMP increased rapidly, reaching a maximum of twice the basal level 10--45 s after stimulation; after 2--5 min the amount of cAMP had subsided to basal levels. Elevations in cAMP levels were concurrent with, or followed, membrane hyperpolarization (measured by uptake of the lipophilic cation triphenylmethyl phosphonium) and always preceded lysosomal enzyme release and superoxide anion (O2) production. Elevated cAMP levels could be uncoupled from these later events by removal of extracellular divalent cations, replacement of extracellular Na+ with K+ or choline+, and by use of low concentrations of stimulus; each of these conditions virtually abolished lysosomal enzyme release and O2 generation, while leaving the stimulated elevation of cAMP levels unimpaired. Calcium ionophore A23187 did not provoke membrane hyperpolarization, thus uncoupling changes in membrane potential from changes in cAMP levels. These data suggested that cAMP is not a critical component in the earliest steps of stimulus-secretion coupling. Surface stimulation of cells pretreated with prostaglandins E1 or I2 yielded very high levels of cAMP; these high levels may be an important part of the mechanism by which stable prostaglandins inhibit lysosomal enzyme release and O2 generation.