Granulocyte CEACAM3 is a phagocytic receptor of the innate immune system that mediates recognition and elimination of human-specific pathogens.
Granulocyte CEACAM3 is a phagocytic receptor of the innate immune system that mediates recognition and elimination of human-specific pathogens.
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DOI：
10.1084/jem.20030204
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发表时间：
2004-01-05
期刊：
影响因子：
--
通讯作者：
Hauck CR
中科院分区：
文献类型：
--
作者：
Schmitter T;Agerer F;Peterson L;Munzner P;Hauck CR
癌胚抗原相关细胞黏附分子(CEACAM)被几种人类病原体用来固定自己或入侵宿主细胞。有趣的是，人类粒细胞表达一种特殊的异构体CEACAM3，它与CEACAM1和CEACAM6一起参与识别CEACAM结合的微生物。在这里，我们发现CEACAM3可以引导CEACAM结合的奈瑟氏菌、莫拉氏菌和嗜血杆菌的高效、不依赖调理素的吞噬。CEACAM3而不是CEACAM6介导的摄取被显性阴性的小GTP酶RAC所阻断。此外，CEACAM3的结合触发了膜的募集和RAC的GTP负载增加，这在细菌与CEACAM6结合时没有观察到。内化和RAC刺激也可以通过破坏CEACAM3细胞质尾部基于免疫受体酪氨酸激活基序(ITAM)的类似序列的完整性，或者通过干扰使CEACAM3磷酸化的Src家族蛋白酪氨酸激酶来抑制。与干扰CEACAM6相比，阻断CEACAM3介导的事件降低了原代人粒细胞内化和消除CEACAM6结合细菌的能力，表明CEACAM3在先天性免疫系统控制人类特有病原体方面发挥了重要作用。
Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are used by several human pathogens to anchor themselves to or invade host cells. Interestingly, human granulocytes express a specific isoform, CEACAM3, that participates together with CEACAM1 and CEACAM6 in the recognition of CEACAM-binding microorganisms. Here we show that CEACAM3 can direct efficient, opsonin-independent phagocytosis of CEACAM-binding Neisseria, Moraxella, and Haemophilus species. CEACAM3- but not CEACAM6-mediated uptake is blocked by dominant-negative versions of the small GTPase Rac. Moreover, CEACAM3 engagement triggers membrane recruitment and increased GTP loading of Rac that are not observed upon bacterial binding to CEACAM6. Internalization and Rac stimulation are also inhibited by compromising the integrity of an immunoreceptor tyrosine-based activation motif (ITAM)–like sequence in the cytoplasmic tail of CEACAM3 or by interference with Src family protein tyrosine kinases that phosphorylate CEACAM3. In contrast to interfering with CEACAM6, blockage of CEACAM3-mediated events reduces the ability of primary human granulocytes to internalize and eliminate CEACAM-binding bacteria, indicating an important role of CEACAM3 in the control of human-specific pathogens by the innate immune system.
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DOI：
10.1006/bbrc.2000.3858
发表时间：
2000-11-30
影响因子：
3.1
作者：
Oikawa, S;Sugiyama, M;Nakazato, H
通讯作者：
Nakazato, H
影响因子：
16
作者：
Ergün, S;Kilic, N;Wagener, C
通讯作者：
Wagener, C
影响因子：
11.4
作者：
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通讯作者：
Meyer, TF
影响因子：
4.8
作者：
Becker-Hapak, M;McAllister, SS;Dowdy, SF
通讯作者：
Dowdy, SF
影响因子：
3.1
作者：
Guignot, J;Peiffer, I;Servin, AL
通讯作者：
Servin, AL