Fever-range hyperthermia dynamically regulates lymphocyte delivery to high endothelial venules
Fever-range hyperthermia dynamically regulates lymphocyte delivery to high endothelial venules
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DOI：
10.1182/blood.v97.9.2727
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发表时间：
2001-05-01
期刊：
影响因子：
20.3
通讯作者：
Repasky, EA
中科院分区：
文献类型：
--
作者：
Evans, SS;Wang, WC;Repasky, EA
发热与急性感染期间存活率的增加有关，尽管其作用机制在很大程度上尚不清楚。这项研究发现了一种出人意料的整合机制的证据，即发热范围内的温度通过增加循环淋巴细胞与特殊的高内皮微静脉(HEV)之间的L-选择素和α-β7整合素依赖的黏附相互作用，刺激淋巴细胞归巢到次级淋巴组织。活体脾淋巴细胞暴露于发热样全身高温(39.8+/-0.2℃，6小时)，在切变条件下，刺激淋巴结和Peyer补片中的L-选择素和α4-β7整合素依赖的淋巴细胞与HEV的黏附。HEV对L-选择素和α4-β7整合素(即外周淋巴结位素和粘膜位置素细胞黏附分子-1)的粘附性也在WBH或与内毒素或松节油诱导的炎症相关的发热反应中增加。在体外培养的淋巴结和Peyer斑片器官培养中，HEV粘附率也有类似的增加，表明局部淋巴组织微环境足以应对高温反应。相反，WBH不能增加非淋巴组织鳞状内皮细胞的粘附性。对α4-β7(Hi)L-选择素(Lo)小鼠TK1细胞和L-选择素(Hi)α4-β7整合素阴性的300.19/L-选择素转基因细胞的归巢分析表明，发热温度导致L-选择素和α4β7整合素依赖于次级淋巴组织的转运增加了3-4倍。因此，通过双峰调节淋巴细胞和内皮细胞的黏附，通过高温增强淋巴细胞对HEV的转运，为促进免疫监视提供了一种新的机制。(血。2001年；97：2727-2733)(C)2001，美国血液病学会。
Fever is associated with increased survival during acute infection, although its mechanism of action is largely unknown. This study found evidence of an unexpectedly integrated mechanism by which fever-range temperatures stimulate lymphocyte homing to secondary lymphoid tissues by increasing L-selectin and alpha4 beta7 integrin-dependent adhesive interactions between circulating lymphocytes and specialized high endothelial venules (HEV). Exposure of splenic lymphocytes in vivo to fever-like whole-body hyperthermia (WBH; 39.8 +/- 0.2 degreesC for 6 hours) stimulated both L-selectin and alpha4 beta7 integrin-dependent adhesion of lymphocytes to HEV under shear conditions in lymph nodes and Peyer patches. The adhesiveness of HEV ligands for L-selectin and alpha4 beta7 integrin (ie, peripheral lymph node addressin and mucosal addressin cell adhesion molecule-1) also increased during WBH or febrile responses associated with lipopolysaccharide-induced or turpentine-induced inflammation. Similar increases in HEV adhesion occurred during hyperthermia treatment of lymph node and Peyer patch organ cultures in vitro, indicating that the local lymphoid tissue microenvironment is sufficient for the hyperthermia response. In contrast, WBH did not augment adhesion in squamous endothelium of nonlymphoid tissues. Analysis of homing of alpha4 beta7(hi) L-selectin(lo) murine TK1 cells and L-selectin(hi) alpha4 beta7 integrin-negative 300.19/L-selectin transfectant cells showed that fever-range temperatures caused a 3- to 4-fold increase in L-selectin and alpha4 beta7 integrin-dependent trafficking to secondary lymphoid tissues. Thus, enhanced lymphocyte delivery to HEV by febrile temperatures through bimodal regulation of lymphocyte and endothelial adhesion provides a novel mechanism to promote immune surveillance. (Blood. 2001; 97:2727-2733) (C) 2001 by The American Society of Hematology.