Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display
Molecular heterogeneity of the vascular endothelium revealed by in vivo phage display
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DOI：
10.1172/jci3008
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发表时间：
1998-07-15
影响因子：
15.9
通讯作者：
Ruoslahti, E
中科院分区：
文献类型：
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作者：
Rajotte, D;Arap, W;Ruoslahti, E
已知血管床在结构和代谢功能上不同，但对其分子多样性知之甚少。我们已经研究了器官特异性分子差异的内皮细胞在各种组织中，通过使用在体内筛选的噬菌体表面上表达的肽库。我们在这里报告说，用这种方法靶向大量组织，在每种情况下，噬菌体选择性地归巢到靶器官。从这些组织中的每一个回收不同的肽基序。相对于噬菌体，归巢到靶器官的富集是3-35倍。对噬菌体选择性归巢于肺、皮肤和胰腺血管的肽序列进行了详细的表征。免疫组织化学显示噬菌体定位于其靶器官的血管中。当测试时，在同源肽存在下阻断噬菌体归巢。通过靶向几种组织，并显示特定归巢可以在每种情况下实现，我们提供的证据表明，器官和组织特异性的分子异质性的血管系统是一个普遍的，甚至可能是普遍的现象。我们的研究结果还表明，这些分子差异可以作为分子地址。
Vascular beds are known to differ in structure and metabolic function, but less is known about their molecular diversity. We have studied organ-specific molecular differences of the endothelium in various tissues by using in vivo screening of peptide libraries expressed on the surface of a bacteriophage. We report here that targeting of a large number of tissues with this method yielded, in each case, phage that homed selectively to the targeted organ. Different peptide motifs were recovered from each of these tissues. The enrichment in homing to the target organs relative to an unselected phage was 3-35-fold. Peptide sequences that conferred selective phage homing to the vasculature of lung, skin, and pancreas were characterized in detail, Immunohistochemistry showed that the phage localized in the blood vessels of their target organ. When tested, the phage homing was blocked in the presence of the cognate peptide. By targeting several tissues and by showing that specific homing could be achieved in each case, we provide evidence that organ- and tissue-specific molecular heterogeneity of the vasculature is a general, perhaps even universal, phenomenon. Our results also show that these molecular differences can serve as molecular addresses.