Circulating factors contribute to elevation of intracellular cyclic-3',5'-adenosine monophosphate and depression of superoxide anion production in polymorphonuclear leukocytes following thermal injury.
Circulating factors contribute to elevation of intracellular cyclic-3',5'-adenosine monophosphate and depression of superoxide anion production in polymorphonuclear leukocytes following thermal injury.
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热损伤后，循环因子导致细胞内环状 3,5- 腺苷单磷酸升高和多形核白细胞中超氧阴离子产生减少。
DOI：
10.1002/jlb.52.4.407
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发表时间：
1992
影响因子：
5.5
通讯作者：
Bjornson,HS
中科院分区：
文献类型：
--
作者：
Bjornson,AB;Somers,SD;Knippenberg,RW;Bjornson,HS
我们之前已经证明，在豚鼠模型中，热损伤后多形核白细胞（PMN）的杀菌活性和超氧阴离子（O2−）产生同时受到抑制，杀菌缺陷与细胞内环-3 ′，5 ′-腺苷酸（cAMP）的升高有关。本研究的目的是确定热损伤后中性粒细胞内cAMP升高和O2−产生抑制之间的关系，并确定循环因子在这些变化发展中的参与。在该实验模型中，热损伤后外周PMN中O2−产生的动力学和对甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）和佛波醇肉豆蔻酸酯（PMA）的剂量反应受到抑制。在PMN功能障碍期间获得的血清诱导正常PMN中响应于fMLP的O2−产生的抑制和细胞内cAMP的升高。用非甾体抗炎药（NSAID;吲哚美辛或吡罗昔康）预处理正常PMN可抑制损伤动物血清介导的细胞内cAMP升高，但对在类似条件下观察到的O2−产生抑制无影响。在已知可降低细胞cAMP含量和纠正杀菌缺陷的条件下，用NSAID处理受伤动物的PMN，不能使O2~-产生正常化。利用来自两名热损伤患者的血清进行的研究证实了豚鼠模型中血清介导的细胞内cAMP升高和正常PMN中O2−产生抑制的结果以及NSAID观察到的效应。这些结果表明，循环因素有助于热损伤后PMN细胞内cAMP的升高和O2−产生的抑制。虽然细胞内cAMP的增加可能与O2−产生的抑制有关，但我们的研究结果表明，这些变化之间没有直接联系。
We have previously demonstrated that bactericidal activity and superoxide anion (O2−) production are depressed concomitantly in polymorphonuclear leukocytes (PMNs) following thermal injury in a guinea pig model, and the bactericidal defect is related to elevation of intracellular cyclic‐3′,5′‐adenosine monophosphate (cAMP). The purpose of the present investigation was to determine the relationship between elevation of intracellular cAMP and depression of O2−production in PMNs following thermal injury and determine the involvement of circulating factors in the development of these alterations. The kinetics of O2−production and dose responses to formylmethionyl‐leucyl‐phenylalanine (fMLP) and phorbol myristate acetate (PMA) were depressed in peripheral PMNs following thermal injury in this experimental model. Sera obtained during the period of PMN dysfunction induced depression of O2−production in response to fMLP and elevation of intracellular cAMP in normal PMNs. Pretreatment of normal PMNs with nonsteroidal anti‐inflammatory drugs (NSAID; in‐ domethacin or piroxicam) inhibited the elevation of intracellular cAMP mediated by sera from the injured animals but had no effect on the depression of O2−production observed under similar conditions. Treatment of PMNs from injured animals with NSAID under conditions known to reduce the cAMP content of the cells and correct the bactericidal defect did not normalize O2~ production. Studies utilizing sera from two thermally injured patients confirmed findings in the guinea pig model of serum‐mediated elevation of intracellular cAMP and depression of O2−production in normal PMNs and effects observed with NSAID. These results suggest that circulating factors contribute to the elevation of intracellular cAMP and depression of O2−production in PMNs following thermal injury. Whereas the increase in intracellular cAMP may be involved in the depression of O2−production, our results suggest that there is not a direct link between these alterations.