Published online before print April 14, 2003, doi: 10.1161/01.CIR.0000062687.80186.A0
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(Circulation. 2003;107:2140.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Role of Interferon-
in Hypercholesterolemia-Induced Leukocyte–Endothelial Cell Adhesion
From the Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, La.
Correspondence to D. Neil Granger, PhD, Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 E Kings Highway, Shreveport, LA 71130-3932. E-mail dgrang{at}lsuhsc.edu
Background— A T-cell–mediated inflammatory response occurs in the microcirculation during acute hypercholesterolemia. The objective of this study was to define the contribution of T-lymphocyte–derived interferon-
(IFN-) to the leukocyte–endothelial cell adhesion induced by hypercholesterolemia.
Methods and Results— Intravital videomicroscopy was used to quantify the adhesion and emigration of leukocytes and oxidant stress (dihydrorhodamine [DHR] oxidation) in cremasteric venules. Wild-type (WT), IFN--/-, and severe combined immunodeficiency (SCID) mice were placed on either a normal (ND) or high-cholesterol (HC) diet for 2 weeks. WT-HC mice exhibited exaggerated adhesion and emigration of leukocytes and enhanced DHR oxidation compared with WT-ND. The exaggerated adhesion responses and increased DHR oxidation were not seen in IFN--/-–HC mice. SCID-HC mice also exhibited attenuated inflammatory responses compared with WT-HC. Reconstitution of either SCID-HC or IFN--/-–HC mice with WT-HC splenocytes restored the inflammatory responses, whereas reconstitution of SCID-HC with IFN--/-–HC splenocytes did not. The HC-induced oxidant stress was restored in IFN--/-–HC mice reconstituted with WT-HC splenocytes.
Conclusions— These findings implicate IFN- as a cause of the inflammatory phenotype that is assumed by the microvasculature of hypercholesterolemic mice and suggest that T lymphocytes are a major source of this proinflammatory cytokine.
Key Words: leukocytes • endothelium • hypercholesterolemia • lymphocytes
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