Cytokine and adhesion molecule expression in primary human endothelial cells stimulated with fever-range hyperthermia.
Migration of blood-borne lymphocytes into lymphoid tissues and sites of inflammation is initiated by vascular adhesion molecules and proinflammatory cytokines. Previous in vivo studies have shown that febrile temperatures dynamically stimulate adhesion in differentiated high endothelial venules (HEV), which are portals for lymphocyte extravasation. This report examines the direct effect of fever-range hyperthermia on the expression of adhesion molecules and cytokines by primary cultured endothelial cells. In both macrovascular (HUVEC) and microvascular (HMVEC) endothelial cells, fever-range hyperthermia (40 degrees C for 6-12 h) did not affect expression of adhesion molecules (ICAM-1, E-selectin, VCAM-1, P-selectin, PECAM-1, PNAd, MAdCAM-1), cytokine release (IL-1beta, TNF-alpha, IFN-gamma, IL-6, IL-11, IL-12, IL-13), or chemokine secretion (IL-8, RANTES, MCP-1, MIP-1beta, MIG). This is in contrast to the stimulatory effects of TNF-alpha or 43 degrees C heat shock. However, a novel role for fever-range hyperthermia was identified in augmenting actin polymerization in cultured endothelial cells and enhancing the ability of endothelial-derived factors to transactivate the alpha4beta7 integrin lymphocyte homing receptor. These findings provide insight into the tightly regulated effects of fever-range hyperthermia that exclude induction of adhesion in non-activated endothelium of normal blood vessels. Through these mechanisms, it is proposed that febrile temperatures associated with infection or clinical hyperthermia avoid the unproductive exodus of lymphocytes to non-involved extralymphoid tissues while simultaneously promoting lymphocyte delivery to sites of immune activation.
Shah
A
A
Department of Immunology, Roswell Park Cancer Institute, Carlton & Elm Streets, Buffalo, New York 14263, USA.
Unger
E
E
Bain
M D
MD
Bruce
R
R
Bodkin
J
J
Ginnetti
J
J
Wang
W C
WC
Seon
B
B
Stewart
C C
CC
Evans
S S
SS
D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005334:Fever / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D011108:Polymers / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism
D000199:Actins; D015815:Cell Adhesion Molecules; D016207:Cytokines; D011108:Polymers; D016201:Receptors, Lymphocyte Homing