Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis.
Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis.
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DOI：
10.1084/jem.192.3.433
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发表时间：
2000-08-07
期刊：
影响因子：
--
通讯作者：
Snyderman R
中科院分区：
文献类型：
--
作者：
Haribabu B;Verghese MW;Steeber DA;Sellars DD;Bock CB;Snyderman R
白三烯衍生自花生四烯酸，并作为炎症和速发型超敏反应的介质。白三烯B4（LTB 4）和白三烯C4（LTC 4）分别通过G蛋白偶联受体LTB 4受体（BLTR）和Cys-LTR起作用。为了研究BLTR的生理作用，我们用BLTR基因的靶向破坏产生小鼠。BLTR缺陷小鼠（BLTR−/−）发育正常，没有明显的造血异常。BLTR−/−小鼠的腹膜中性粒细胞对炎症介质C5 a和血小板活化因子（PAF）表现出正常反应，但对LTB 4的钙动员或趋化性没有反应。此外，LTB 4在对照组中引起腹膜中性粒细胞流入，但在BLTR−/−小鼠中没有。因此，BLTR是小鼠中LTB 4诱导的炎症的唯一受体。在BLTR−/−小鼠中，腹膜炎模型和花生四烯酸引起的急性耳部炎症中的神经元内流显著减少。在小鼠中，静脉注射PAF可诱导立即致死的过敏反应。令人惊讶的是，雌性BLTR−/−小鼠相对于PAF诱导过敏反应的雄性小鼠（1/11）显示出选择性存活（6/9; P = 0.002）。这些结果证明了BLTR在白三烯介导的急性炎症中的作用，以及PAF诱导的过敏反应中意外的性别相关参与。
Leukotrienes are derived from arachidonic acid and serve as mediators of inflammation and immediate hypersensitivity. Leukotriene B4 (LTB4) and leukotriene C4 (LTC4) act through G protein–coupled receptors LTB4 receptor (BLTR) and Cys-LTR, respectively. To investigate the physiological role of BLTR, we produced mice with a targeted disruption of the BLTR gene. Mice deficient for BLTR (BLTR−/−) developed normally and had no apparent hematopoietic abnormalities. Peritoneal neutrophils from BLTR−/− mice displayed normal responses to the inflammatory mediators C5a and platelet-activating factor (PAF) but did not respond to LTB4 for calcium mobilization or chemotaxis. Additionally, LTB4 elicited peritoneal neutrophil influx in control but not in BLTR−/− mice. Thus, BLTR is the sole receptor for LTB4-induced inflammation in mice. Neutrophil influx in a peritonitis model and acute ear inflammation in response to arachidonic acid was significantly reduced in BLTR−/− mice. In mice, intravenous administration of PAF induces immediate lethal anaphylaxis. Surprisingly, female BLTR−/− mice displayed selective survival (6 of 9; P = 0.002) relative to male (1 of 11) mice of PAF-induced anaphylaxis. These results demonstrate the role of BLTR in leukotriene-mediated acute inflammation and an unexpected sex-related involvement in PAF-induced anaphylaxis.
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DOI：
10.1084/jem.188.6.1063
发表时间：
1998-09-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Huang WW;Garcia-Zepeda EA;Sauty A;Oettgen HC;Rothenberg ME;Luster AD
通讯作者：
Luster AD
DOI：
10.1084/jem.184.4.1483
发表时间：
1996-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
7
作者：
PISETSKY, DS
通讯作者：
PISETSKY, DS
影响因子：
64.8
作者：
Yokomizo, T;Izumi, T;Shimizu, T
通讯作者：
Shimizu, T
影响因子：
64.8
作者：
DAHLEN, SE;HEDQVIST, P;SAMUELSSON, B
通讯作者：
SAMUELSSON, B