Rapid chemokine secretion from endothelial cells originates from 2 distinct compartments

Rapid chemokine secretion from endothelial cells originates from 2 distinct compartments
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DOI:
10.1182/blood-2003-08-2891
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发表时间:
2004-07-15
期刊:
影响因子:
20.3
通讯作者:
Haraldsen, G
Haraldsen, G
中科院分区:
医学1区
文献类型:
--
作者:
Oynebråten, I;Bakke, O;Haraldsen, G

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中性粒细胞趋化因子白介素8(IL-8)储存于内皮细胞(ECs)的韦氏小体(WPB)中,经促分泌剂、组胺或凝血酶刺激后可迅速释放出来。通过这种方式,IL-8可以使白细胞快速募集到炎症部位。为了探索可能吸引其他白细胞亚群的EC来源的趋化因子的可能储存,我们检测了生长相关癌基因α(GROAlpha)、单核细胞趋化蛋白-1(MCP-1)、嗜酸性粒细胞趋化因子-3、干扰素-γ诱导蛋白10(IP-10)以及调节激活、正常T细胞表达和分泌(RANTES)的细胞内定位和分泌反应性。Eoaxin-3、GROAlpha和MCP-1从内皮细胞迅速释放,而T细胞诱导剂RANTES和IP-10的释放对分泌剂不敏感。此外,在前3种趋化因子中,只有嗜酸性粒细胞趋化因子-3储存在WPBs中。GROAlpha和MCP-1主要存在于较小的囊泡中,与分选到不同的组胺反应间隔兼容,这在内皮细胞中已被描述,尽管没有报道含有趋化因子。总之,我们认为,趋化因子的快速释放仅限于那些主要招募天然免疫系统中的白细胞的细胞,而它们在内皮细胞中的储存并不局限于WPB隔室。(C)2004年,由美国血液病学会提供。
The neutrophil-attracting chemokine interleukin 8 (IL-8) is stored in the Weibel-Palade body (WPB) of endothelial cells (ECs) from which it can be rapidly released after exposure to the secretagogues histamine or thrombin. In this manner, IL-8 may enable rapid recruitment of leukocytes to inflammatory sites. To explore the possible storage of EC-derived chemokines that may attract other subsets of leukocytes, we examined the intracellular localization and secretagogue responsiveness of growth-related oncogene alpha, (GROalpha), monocyte chemoattractant protein-1 (MCP-1), eotaxin-3, interferon-gamma-inducible protein 10 (IP-10), and regulated on activation, normal T-cell expressed and secreted (RANTES). While eotaxin-3, GROalpha, and MCP-1 were rapidly released from ECs, the release of the T-cell attractors RANTES and IP-10 was not sensitive to the secretagogues. Moreover, of the 3 former chemokines, only eotaxin-3 was stored in WPBs. GROalpha and MCP-1 resided mainly in smaller vesicles compatible with sorting to a different, histamine-responsive compartment, which has been described in ECs although not reported to contain chemokines. In conclusion, we propose that rapid release of chemokines is restricted to those primarily recruiting leukocytes of the innate immune system, and that their storage in ECs is not restricted to the WPB compartment. (C) 2004 by The American Society of Hematology.