Dermal and pulmonary inflammatory disease in E-selectin and P-selectin double-null mice is reduced in triple-selectin-null mice
Dermal and pulmonary inflammatory disease in E-selectin and P-selectin double-null mice is reduced in triple-selectin-null mice
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DOI：
10.1182/blood.v98.3.727
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发表时间：
2001-08-01
期刊：
影响因子：
20.3
通讯作者：
Beaudet, AL
中科院分区：
文献类型：
--
作者：
Collins, RG;Jung, U;Beaudet, AL
在炎症反应的初始阶段，白细胞；由于内皮细胞和白细胞分子之间的粘附相互作用，沿内皮细胞表面边缘和滚动。为了评估3种选择素（E， L和P）在白细胞滚动和迁移中的作用，将L-选择素的零突变引入先前描述的具有E-选择素和P-选择素基因零突变的胚胎干细胞（E/P双突变体），以产生三选择素零小鼠（E-选择素，L-选择素和P-选择素[E/L/P]三重突变体）。三选择素纯合突变小鼠是可存活和可生育的，很少发生E/P双突变小鼠所特有的严重粘膜皮肤感染或肺部炎症。外周中性粒细胞荧光活化细胞分选分析显示，三突变小鼠中l-选择素的表面表达未被检测到。病理研究显示有中度的宫颈淋巴结病变和淋巴浆细胞浸润，但这些病变不像E/P双突变小鼠那么广泛。巯基乙酸盐引起的腹膜炎期间，中性粒细胞迁移在4、8和24小时显著减少（分别为野生型值的35%、65%和46%）。体外置瘤后6小时内，无论是否添加肿瘤坏死因子，肌内活体显微镜显示几乎没有滚动。少量的残余滚动依赖于α 4-整联素。E/P双突变小鼠发生皮肤和肺部疾病，而E/L/P三突变小鼠没有发生，这表明缺乏L-选择素改变了E/P突变体的炎症反应。(C) 2001年由美国血液学会出版。
In the initial phase of an inflammatory response, leukocytes; marginate and roll along the endothelial surface as a result of adhesive interactions between molecules on the endothelial cells and leukocytes. To evaluate the role of the 3 selectins (E, L, and P) in leukocyte rolling and emigration, a null mutation for L-selectin was introduced into previously described embryonic stem cells with null mutations in the genes for both E-selectin and P-selectin (E/P double mutants) to produce triple-selectin-null mice (E-selectin, L-selectin, and P-selectin [E/L/P] triple mutants). Triple-selectin homozygous mutant mice are viable and fertile and only rarely develop the severe mucocutaneous infections or pulmonary inflammation characteristic of E/P double-mutant mice. Surface expression of L-selectin was undetectable in triple-mutant mice on fluorescence-activated cell-sorter analysis of peripheral neutrophils. Pathological studies revealed moderate cervical lymphadenopathy and lymphoplasmacytic infiltrate, but these were less extensive than in E/P double-mutant mice. Neutrophil emigration during thioglycolate-induced peritonitis was significantly reduced at 4, 8, and 24 hours (35%, 65%, and 46% of wild-type values, respectively). Intravital microscopy of the cremaster muscle revealed almost no rolling at times up to 6 hours after exteriorization, with or without addition of tumor necrosis factor alpha. The small amount of residual rolling was dependent on alpha4-integrin. The occurrence of skin and pulmonary disease in E/P double-mutant mice but not E/L/P triple-mutant mice suggests that deficiency of L-selectin alters the inflammatory response in E/P mutants. (C) 2001 by The American Society of Hematology.