DIRECT OBSERVATION OF SUBSTANCE-P-INDUCED INTERNALIZATION OF NEUROKININ-1 (NK1) RECEPTORS AT SITES OF INFLAMMATION
DIRECT OBSERVATION OF SUBSTANCE-P-INDUCED INTERNALIZATION OF NEUROKININ-1 (NK1) RECEPTORS AT SITES OF INFLAMMATION
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DOI：
10.1073/pnas.91.19.8964
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发表时间：
1994-09-13
影响因子：
11.1
通讯作者：
MCDONALD, DM
中科院分区：
文献类型：
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作者：
BOWDEN, JJ;GARLAND, AM;MCDONALD, DM
P物质（SP）可通过与内皮细胞表面的神经激肽1型（NK 1）受体结合而引起炎症部位的血浆渗漏。配体结合后的内化可以减少细胞表面的NK 1受体的数量，从而参与对SP的炎症反应的脱敏和再敏化。通过使用受体的抗体，我们直接观察到SP诱导的NK 1受体内化到大鼠气管粘膜毛细血管后微静脉内皮细胞的内体中。在不存在SP的情况下，每个内皮细胞平均存在15个免疫反应性内体。静脉注射SP后，免疫反应性核内体的数量达到峰值，在107每细胞在3分钟，并逐渐恢复到基线的120分钟。在平行实验中，我们观察到，当培养的细胞转染的NK 1受体暴露于罗丹明-SP和抗体的NK 1受体的细胞外标志表位，SP与受体抗体内化。无论是在培养的细胞和在完整的动物的内皮细胞中，提示SP诱导的内化伴随着快速，持久的脱敏SP。这些研究表明，由内皮细胞的NK 1受体的内化可能是一种机制，限制在炎症部位的血浆泄漏量。
Substance P (SP) can cause plasma leakage at sites of inflammation by binding to neurokinin type 1 (NK1) receptors on the surface of endothelial cells. Internalization after ligand binding could reduce the number of NK1 receptors on the cell surface and thus participate in the desensitization and resensitization of the inflammatory response to SP. By using an antibody to the receptor, we directly observed SP-induced internalization of NK1 receptors into endosomes in endothelial cells of postcapillary venules in the rat tracheal mucosa. In the absence of SP, an average of 15 immunoreactive endosomes were present per endothelial cell. After an intravenous injection of SP, the number of immunoreactive endosomes peaked at 107 per cell at 3 min and gradually returned to the baseline by 120 min. In parallel experiments we observed that when cultured cells transfected with the NK1 receptor were exposed to rhodamine-SP and an antibody to an extracellular Flag epitope of the NK1 receptor, the SP was internalized with the receptor antibody. Both in the cultured cells and in the endothelial cells of intact animals, the prompt SP-induced internalization was accompanied by rapid, long-lasting desensitization to SP. These studies suggest that internalization of NK1 receptors by endothelial cells may be one of the mechanisms that limit the amount of plasma leakage at sites of inflammation.