Heterogeneity of expression of E- and P-selectins in vivo
Heterogeneity of expression of E- and P-selectins in vivo
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DOI：
10.1161/01.res.79.3.560
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发表时间：
1996-09-01
影响因子：
20.1
通讯作者：
Granger, DN
中科院分区：
文献类型：
--
作者：
Eppihimer, MJ;Wolitzky, B;Granger, DN
一种新的技术，涉及放射性标记的单克隆抗体被用来表征和比较E-和P-选择素的表达对未受刺激的，组胺的挑战，和内毒素的挑战在小鼠的各种组织中的内皮细胞。在非刺激条件下，E-选择素是不存在的所有器官，但P-选择素的显着表达中观察到的几个器官。组胺诱导P-选择素的快速时间依赖性上调，在肠系膜和肺中观察到最大的反应。早在组胺注射后5分钟，P-选择素表达就出现显著的倍数升高，并保持升高至1小时。组胺诱导的P-选择素上调被抑制H-1受体拮抗剂苯海拉明，而H-2受体拮抗剂西咪替丁没有效果。内毒素（脂多糖[LPS]）也诱导P-选择素的时间依赖性表达，内毒素给药后4 - 8小时达到最大值。LPS诱导的P-选择素的上调在心脏和胃中最大，其表现出不显著的P-选择素的组成性表达。LPS还诱导E-选择素的时间依赖性上调，最大表达发生在腹膜内给药后3至5小时。肺和小肠对LPS攻击的反应最大。组胺给药不影响E-选择素在任何组织中的表达。使用E-和P-选择素缺陷小鼠来测试单克隆抗体在未刺激的、组胺激发的和LPS刺激的组织中结合的特异性。在相应缺陷小鼠中未观察到放射性标记的E-选择素和P-选择素单克隆抗体的血管结合。这些研究结果表明，P-选择素是组成性表达的血管内皮细胞在一些组织的小鼠和组胺和内毒素诱导的P-选择素表达的幅度和时间过程中有显着的区域差异。相比之下，E-选择素似乎不存在于未刺激的血管内皮上，但在大多数组织中给予内毒素后3小时内上调。
A novel technique involving radiolabeled monoclonal antibodies was used to characterize and compare the expression of E- and P-selectin on unstimulated, histamine-challenged, and endotoxin-challenged endothelial cells in various tissues of the mouse. Under unstimulated conditions, E-selectin was absent in all organs, but significant expression of P-selectin was observed in several organs. Histamine induced a rapid time-dependent upregulation of P-selectin, with the largest responses observed in mesentery and lung. Significant fold elevations in P-selectin expression occurred as early as 5 minutes after the histamine injection and remained elevated up to 1 hour. Histamine-induced P-selectin upregulation was inhibited by the H-1 receptor antagonist diphenhydramine, whereas the H-2 receptor antagonist cimetidine had no effect. Endotoxin (lipopolysaccharide [LPS]) also induced a time-dependent expression of P-selectin that reached a maximum between 4 and 8 hours after endotoxin administration. LPS-induced upregulation of P-selectin was greatest in heart and stomach, which exhibited insignificant constitutive expression of P-selectin. LPS also induced a time-dependent upregulation of E-selectin, with maximal expression occurring 3 to 5 hours after intraperitoneal administration. The lung and small intestine exhibited the largest responses to LPS challenge. Histamine administration did not affect E-selectin expression in any tissue. E- and P-selectin-deficient mice were used to test the specificity of monoclonal antibody binding in unstimulated, histamine-challenged, and LPS-stimulated tissues. Vascular binding of the radiolabeled E-selectin and P-selectin monoclonal antibodies was not observed in the respective deficient mice. These findings suggest that P-selectin is constitutively expressed on vascular endothelium in some tissues of the mouse and that there are significant regional differences in the magnitude and time course of histamine- and endotoxin-induced P-selectin expression. In contrast, E-selectin appears to be absent on unstimulated vascular endothelium but is upregulated within 3 hours after the administration of endotoxin in most tissues.