Fever-range hyperthermia stimulates alpha4beta7 integrin-dependent lymhocyte-endothelial adhesion
Publishing house: International Journal of Hyperthermia
Main author: S.S. Evans
Other authors: M. D. Bain, W. C. Wang
Date: 1999-05-28
ISSN print: 0265-6736 / ISSN online: 1464-5157
Language: english
Publication class: Review article
Abstract: Migration of blood-borne lymphocytes into lymphoid tissues is initiated by the L-selectin and alfa4beta7 integrin adhesion molecules. Previous studies have shown that L-selectin adhesion molecules. Previous studies have shown that L-selectin adjesion 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 alfa4beta7 integrin. Fever-range hyperthermia treatment in vitro (40°C, 12 h) of murine TK1 lymphoma cells and human peripheral blood lymphocytes (PBL) stimulates alfa4beta7 integrin-dependent adhesion to high endothelial venules (HEV) in Peyer’s patch and mesentric lymph node frozen sections. TK1 cells are alfa4beta7hi L-selectinlo, allowing for the analysis of alfa4beta7 integrin without contributions from L-selectin. Adhesion was further shown to involve alfa4beta7 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 alfa4beta7 integrin-mediated aggregation of TK1 cells. In sharp contrast, hyperthermia fails to increase alfa4beta7 integrin adhesion to fibrconectin by TK1 cells. Expression of the alfa4beta7 heterodimer on TK1 cells or human PBL is not altered by hyperthermia, suggesting that hyperthermia stimulates adhesion by enhancingalfa4beta7 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 alfa4beta7 integrin-dependent homing of immune effector cells to lymphoid tissues.
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