Abstract
Fever is an evolutionarily conserved response during acute inflammation, although its physiological benefit is poorly understood. Here we show thermal stress in the range of fever temperatures increased the intravascular display of two 'gatekeeper' homing molecules, intercellular adhesion molecule 1 (ICAM-1) and CCL21 chemokine, exclusively in high endothelial venules (HEVs) that are chief portals for the entry of blood-borne lymphocytes into lymphoid organs. Enhanced endothelial expression of ICAM-1 and CCL21 was linked to increased lymphocyte trafficking across HEVs. A bifurcation in the mechanisms controlling HEV adhesion was demonstrated by evidence that the thermal induction of ICAM-1 but not of CCL21 involved an interleukin 6 trans-signaling pathway. Our findings identify the 'HEV axis' as a thermally sensitive alert system that heightens immune surveillance during inflammation by amplifying lymphocyte trafficking to lymphoid organs.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Adhesion / immunology
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Chemokine CCL21
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Chemokines, CC / immunology
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Chemokines, CC / metabolism
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Chemotaxis, Leukocyte / immunology*
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Electrophoresis, Polyacrylamide Gel
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Endothelium, Vascular / immunology*
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Endothelium, Vascular / metabolism
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Female
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Fever / immunology*
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Flow Cytometry
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Fluorescent Antibody Technique
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Immunoblotting
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Intercellular Adhesion Molecule-1 / immunology
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Intercellular Adhesion Molecule-1 / metabolism
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Interleukin-6 / immunology*
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Interleukin-6 / metabolism
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Lymph Nodes / blood supply
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Lymph Nodes / cytology
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Lymph Nodes / immunology
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Lymphocytes / immunology*
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Mice
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Signal Transduction / immunology*
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Stress, Physiological / immunology
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Stress, Physiological / metabolism
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Venules / immunology
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Venules / metabolism
Substances
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Ccl21c protein, mouse
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Chemokine CCL21
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Chemokines, CC
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Interleukin-6
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Intercellular Adhesion Molecule-1