LIPOXIN FORMATION DURING HUMAN NEUTROPHIL-PLATELET INTERACTIONS - EVIDENCE FOR THE TRANSFORMATION OF LEUKOTRIENE-A4 BY PLATELET 12-LIPOXYGENASE INVITRO
LIPOXIN FORMATION DURING HUMAN NEUTROPHIL-PLATELET INTERACTIONS - EVIDENCE FOR THE TRANSFORMATION OF LEUKOTRIENE-A4 BY PLATELET 12-LIPOXYGENASE INVITRO
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DOI：
10.1172/jci114503
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发表时间：
1990-03-01
影响因子：
15.9
通讯作者：
SHEPPARD, KA
中科院分区：
文献类型：
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作者：
SERHAN, CN;SHEPPARD, KA
人外周血中的中性粒细胞可能在几种情况下与血小板发生物理作用，包括止血、炎症和各种血管疾病。脂氧合酶(LO)衍生产物的作用与这些事件有关；因此，我们研究了人类中性粒细胞和血小板共孵育过程中脂氧素的形成。同时将FMLP和凝血酶加入到这些细胞的共孵育中会导致脂氧素A4和脂氧素B4的形成，这一点通过反相高压液相色谱进行监测。无论是刺激还是细胞类型都不能单独诱导这些产物的形成。当传递信号的候选分子白三烯A4(LTA4)加入到血小板中时，就形成了脂素。在无细胞的100000克血小板裂解物上清液中，LTA4在显示12-LO活性的同时，也转化为脂素。LO抑制剂秦皮乙素可抑制脂氧素的血小板生成，并对钙离子的螯合作用部分敏感，而乙酰水杨酸和消炎痛均不能显著抑制脂氧素的生成。相比之下，中性粒细胞不会将LTA4转化为脂蛋白。无细胞的100000克中性粒细胞裂解物上清液将LTA4转化为LTB4。这些结果表明，中性粒细胞与血小板的相互作用可以导致内源性脂氧素的形成，并为血小板12-LO在LTA4形成脂氧素的过程中提供了作用。
Human neutrophils from peripheral blood may physically interact with platelets in several settings including hemostasis, inflammation, and a variety of vascular disorders. A role for lipoxygenase (LO)-derived products has been implicated in each of these events; therefore, we investigated the formation of lipoxins during coincubation of human neutrophils and platelets. Simultaneous addition of FMLP and thrombin to coincubations of these cells led to formation of both lipoxin A4 and lipoxin B4, which were monitored by reversed-phase high pressure liquid chromatography. Neither stimulus nor cell type alone induced the formation of these products. When leukotriene A4 (LTA4), a candidate for the transmitting signal, was added to platelets, lipoxins were formed. In cell-free 100,000 g supernatants of platelet lysates, while displayed 12-LO activity, LTA4 was also transformed to lipoxins. Platelet formation of lipoxins was inhibited by the LO inhibitor esculetin and partially sensitive to chelation of Ca2+, while neither acetylsalicylic acid nor indomethacin significantly inhibited their generation. In contrast, neutrophils did not transform LTA4 to lipoxins. Cell-free 100,000 g supernatants of neutrophil lysates converted LTA4 to LTB4. These results indicate that neutrophil-platelet interactions can lead to the formation of lipoxins from endogenous sources and provide a role for platelet 12-LO in the formation of lipoxins from LTA4.