Thermal facilitation of lymphocyte trafficking involves temporal induction of intravascular ICAM-1.
OBJECTIVE
Fever is associated with improved survival, although its beneficial mechanisms are poorly understood. Previous studies indicate that the thermal element of fever augments lymphocyte migration across high endothelial venules (HEVs) of lymphoid organs by increasing the intravascular display of a gatekeeper trafficking molecule, intercellular adhesion molecule-1 (ICAM-1). Here, we evaluated the spatio-temporal relationship between the thermal induction of intravascular ICAM-1 and lymphocyte trafficking.


METHODS
Intravascular ICAM-1 density was quantified by immunofluorescence staining in mice exposed to fever-range whole-body hyperthermia (39.5+/-0.5 degrees C). ICAM-1-dependent lymphocyte trafficking was measured in short-term homing assays.


RESULTS
A linear relationship was observed between the duration of heat treatment and intravascular ICAM-1 density in HEVs with maximal responses requiring sustained (i.e., five hours) thermal stress. Circulating lymphocytes were found to sense incremental changes in ICAM-1 on HEVs, such that trafficking is proportional to the intravascular density of ICAM-1. We further identified a hydroxamate-sensitive shedding mechanism that restores ICAM-1 expression to homeostatic levels following the cessation of thermal stress.


CONCLUSIONS
The time-dependent response to thermal stress indicates that ICAM-1 density governs the efficiency of lymphocyte interactions with HEVs in vivo. These studies highlight the dynamic role of the microcirculation in promoting immune surveillance during febrile inflammatory responses.
Chen
Qing
Q
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Appenheimer
Michelle M
MM
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Muhitch
Jason B
JB
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Fisher
Daniel T
DT
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Clancy
Kristen A
KA
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Miecznikowski
Jeffery C
JC
Biostatistics, Roswell Park Cancer Institute, Buffalo, New York, USA.
Wang
Wan-Chao
WC
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA.
Evans
Sharon S
SS
Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA.
D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D005334:Fever / Q000276:immunology*; D018882:Heat Stress Disorders / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000276:immunology; D014699:Venules / Q000276:immunology
D018799:Intercellular Adhesion Molecule-1