Differential regulation of human and murine P-selectin expression and function in vivo.
Differential regulation of human and murine P-selectin expression and function in vivo.
复制标题
DOI：
10.1084/jem.20101545
复制
发表时间：
2010-12-20
期刊：
影响因子：
--
通讯作者：
McEver RP
中科院分区：
文献类型：
--
作者：
Liu Z;Miner JJ;Yago T;Yao L;Lupu F;Xia L;McEver RP
人P-选择素在转基因小鼠中的基础表达和诱导表达与鼠P-选择素不同，导致不同的功能。白细胞在P-选择素从分泌颗粒动员到血小板和内皮细胞表面后在其上滚动。肿瘤坏死因子（TNF）、IL-1β和脂多糖可增加鼠内皮细胞P-选择素的合成，但对人内皮细胞无影响。为了探索这种基因调控差异的生理意义，我们制作了携带人类Selp基因的转基因小鼠，并将它们与缺乏鼠P-选择素（Selp-/-）的小鼠杂交。转基因小鼠在血小板、内皮细胞和巨噬细胞中组成型表达人P-选择素。P-选择素介导的中性粒细胞迁移到转基因和野生型（WT）小鼠的炎症腹膜。白细胞在人或鼠的P-选择素上、在活化的鼠血小板上和在受到创伤的提睾肌的小静脉中滚动相似。然而，TNF增加小鼠P-选择素在小静脉，减缓滚动和增加粘附，而它减少人类P-选择素，加速滚动和减少粘附。P-和E-选择素介导WT小鼠皮肤的基底滚动，但E-选择素主导转基因小鼠的滚动。在接触性超敏反应过程中，小鼠P-选择素信使（m）RNA上调，P-选择素是白细胞募集所必需的。然而，人P-选择素mRNA下调，P-选择素对白细胞募集的贡献要小得多。这些研究结果揭示了在功能上显着差异的基础和诱导表达的人类和小鼠P-选择素在体内。
Basal and inducible expression of human P-selectin in transgenic mice differs from that of murine P-selectin, resulting in distinct functions. Leukocytes roll on P-selectin after its mobilization from secretory granules to the surfaces of platelets and endothelial cells. Tumor necrosis factor (TNF), IL-1β, and lipopolysaccharide increase synthesis of P-selectin in murine but not in human endothelial cells. To explore the physiological significance of this difference in gene regulation, we made transgenic mice bearing the human Selp gene and crossed them with mice lacking murine P-selectin (Selp−/−). The transgenic mice constitutively expressed human P-selectin in platelets, endothelial cells, and macrophages. P-selectin mediated comparable neutrophil migration into the inflamed peritoneum of transgenic and wild-type (WT) mice. Leukocytes rolled similarly on human or murine P-selectin on activated murine platelets and in venules of the cremaster muscle subjected to trauma. However, TNF increased murine P-selectin in venules, slowing rolling and increasing adhesion, whereas it decreased human P-selectin, accelerating rolling and decreasing adhesion. Both P- and E-selectin mediated basal rolling in the skin of WT mice, but E-selectin dominated rolling in transgenic mice. During contact hypersensitivity, murine P-selectin messenger (m) RNA was up-regulated and P-selectin was essential for leukocyte recruitment. However, human P-selectin mRNA was down-regulated and P-selectin contributed much less to leukocyte recruitment. These findings reveal functionally significant differences in basal and inducible expression of human and murine P-selectin in vivo.
登录
查看更多内容
DOI：
10.1084/jem.20082502
发表时间：
2009-04-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gossens K;Naus S;Corbel SY;Lin S;Rossi FM;Kast J;Ziltener HJ
通讯作者：
Ziltener HJ
影响因子：
64.5
作者：
JOHNSTON, GI;COOK, RG;MCEVER, RP
通讯作者：
MCEVER, RP
DOI：
10.1073/pnas.95.24.14423
发表时间：
1998-11-24
影响因子：
11.1
作者：
Frenette, PS;Subbarao, S;Wagner, DD
通讯作者：
Wagner, DD
影响因子：
15.9
作者：
GROBER, JS;BOWEN, BL;STOOLMAN, LM
通讯作者：
STOOLMAN, LM
DOI：
10.1006/bbrc.1995.1643
发表时间：
1995-05-05
影响因子：
3.1
作者：
BISCHOFF, J;BRASEL, C
通讯作者：
BRASEL, C