Fever-range hyperthermia stimulates α4β7 integrin-dependent lymphocyte-endothelial adhesion
Fever-range hyperthermia stimulates α4β7 integrin-dependent lymphocyte-endothelial adhesion
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DOI：
10.1080/026567300285411
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发表时间：
2000-01-01
影响因子：
3.1
通讯作者：
Wang, WC
中科院分区：
文献类型：
--
作者：
Evans, SS;Bain, MD;Wang, WC
血液携带的淋巴细胞向淋巴组织中的迁移由L-选择素和α 4 β 7整联蛋白粘附分子启动。先前的研究表明，L-选择素粘附是动态调节发热温度。现在报道，发热范围的高热也直接作用于淋巴细胞，以增强α 4 β 7整联蛋白的选定粘附功能。小鼠TK 1淋巴瘤细胞和人外周血淋巴细胞（PBL）的体外发热范围高温治疗（40 ℃，12 h）刺激派伊尔集合淋巴结和肠系膜淋巴结冷冻切片中α 4 β 7整合素依赖性粘附到高内皮微静脉（HEV）。TK 1细胞是α 4 β 7（hi）L-选择素（lo），允许分析α 4 β 7整联蛋白而不需要L-选择素的贡献。使用功能阻断抗体（即DATK 32、HP 2/1、MECA-367）进一步显示粘附涉及α 4 β 7整联蛋白及其内皮反受体粘膜地址素细胞粘附分子-1（MAdCAM-1）。发热范围的高温也促进α 4 β 7整合素介导的TK 1细胞聚集，与此形成鲜明对比的是，高温不能增加TK 1细胞对α 4 β 7整合素与纤连蛋白的粘附。TK 1细胞或人PBL上α 4 β 7异源二聚体的表达不被高温改变，表明高温通过增强α 4 β 7整合素亲合力而不是其细胞表面密度来刺激粘附。这些结果提供了一种机制，即感染或临床高热期间的发热温度可能通过刺激免疫效应细胞向淋巴组织的L-选择素和α 4 β 7整合素依赖性归巢来放大免疫应答。
Migration of blood-borne lymphocytes into lymphoid tissues is initiated by the L-selectin and alpha 4 beta 7 integrin adhesion molecules. Previous studies have shown that L-selectin adhesion is dynamically regulated by febrile temperatures. It is now reported that fever-range hyperthermia also acts directly on lymphocytes to enhance selected adhesive functions of alpha 4 beta 7 integrin. :Fever-range hyperthermia treatment in vitro (40 degrees C, 12 h) of murine TK1 lymphoma cells and human peripheral blood lymphocytes (PBL) stimulates alpha 4 beta 7 integrin-dependent adhesion to high endothelial venules (HEV) in Peyer's patch and mesenteric lymph node frozen sections. TK1 cells are alpha 4 beta 7(hi) L-selectin(lo), allowing for the analysis of alpha 4 beta 7 integrin without contributions from L-selectin. Adhesion was further shown to involve alpha 4 beta 7 integrin and its endothelial counter-receptor, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) using function-blocking antibodies (i.e. DATK32, HP2/1, MECA-367). Fever-range hyperthermia also promotes alpha 4 beta 7 integrin-mediated aggregation of TK1 cells, In sharp contrast, hyperthermia fails to increase alpha 4 beta 7 integrin adhesion to fibronectin by TK1 cells. Expression of the alpha 4 beta 7 heterodimer on TK1 cells or human PBL is not altered by hyperthermia, suggesting that hyperthermia stimulates adhesion by enhancing alpha 4 beta 7 integrin avidity rather than its cell surface density. These results provide a mechanism whereby febrile temperatures during infection or clinical hyperthermia potentially amplify the immune response by stimulating L-selectin and alpha 4 beta 7 integrin-dependent homing of immune effector cells to lymphoid tissues.