TNF-alpha renders human neutrophils responsive to platelet factor 4. Comparison of PF-4 and IL-8 reveals different activity profiles of the two chemokines.
TNF-alpha renders human neutrophils responsive to platelet factor 4. Comparison of PF-4 and IL-8 reveals different activity profiles of the two chemokines.
复制标题
DOI：
10.4049/jimmunol.156.5.1954
复制
发表时间：
1996-03
影响因子：
4.4
通讯作者：
Frank Petersen;Andreas Ludwig;H. Flad;E. Brandt
中科院分区：
文献类型：
--
作者：
Frank Petersen;Andreas Ludwig;H. Flad;E. Brandt
血小板因子4（PF-4）与IL-8一样，是促炎细胞因子的趋化因子超家族的成员。然而，尽管IL-8刺激中性粒细胞功能的能力已得到充分证实，但有关PF-4的报道仍然相互矛盾。在本研究中，我们制备了高度纯化的PF-4，并研究了其诱导趋化性，脱粒，粘附明胶和血浆蛋白，以及细胞内钙水平变化的能力。即使在很宽的浓度范围内，PF-4单独不能诱导PMN的功能变化。然而，与生理相关浓度的TNF-α预孵育或共孵育的中性粒细胞通过选择性动员次级颗粒标志物乳铁蛋白而不是初级颗粒标志物弹性蛋白酶来响应PF-4。与IL-8相反，PMN不需要用细胞松弛素B预处理PF-4诱导的乳铁蛋白胞吐。PF-4与TNF-α的协同作用不是引发现象，因为即使在趋化因子后5分钟加入TNF-α，协同反应也保持不变。与此相反，TNF-α处理的中性粒细胞不响应PF-4的趋化性或细胞内钙离子水平的增加，并没有观察到PF-4的IL-8受体的竞争。我们的研究结果表明PF-4在调节中性粒细胞功能中的机制和生物学作用，这与IL-8和其他α-趋化因子不同。
Platelet factor 4 (PF-4), like IL-8, is a member of the chemokine superfamily of proinflammatory cytokines. However, although the capacity of IL-8 to stimulate functions in neutrophils is well established, reports on PF-4 are still contradictory. In the present study, we have prepared highly purified PF-4 and examined its ability to induce chemotaxis, degranulation, adhesion to gelatin and plasma proteins, and changes in intracellular calcium levels. Even over a broad range of concentrations, PF-4 alone was unable to induce functional changes in PMN. However, neutrophils pre- or co-incubated with physiologically relevant concentrations of TNF-alpha responded to PF-4 by the selective mobilization of the secondary granule marker lactoferrin but not of the primary granule marker elastase. Contrary to IL-8, PMN did not require pretreatment with cytochalasin B for PF-4-induced exocytosis of lactoferrin. The synergistic effect of PF-4 with TNF-alpha was not a priming phenomenon because the cooperative response remained unchanged even when TNF-alpha was added 5 min after the chemokine. In contrast, TNF-alpha-treated PMN did not respond to PF-4 by chemotaxis or by an increase of intracellular calcium levels, and no competition of PF-4 for IL-8 receptors was observed. Our results suggest a mechanism as well as a biologic role of PF-4 in the regulation of neutrophil function, which is different from that of IL-8 and other alpha-chemokines.