Role of interferon-gamma in hypercholesterolemia-induced leukocyte-endothelial cell adhesion.
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-gamma (IFN-gamma) to the leukocyte-endothelial cell adhesion induced by hypercholesterolemia.


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-gamma-/-, 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-gamma-/--HC mice. SCID-HC mice also exhibited attenuated inflammatory responses compared with WT-HC. Reconstitution of either SCID-HC or IFN-gamma-/--HC mice with WT-HC splenocytes restored the inflammatory responses, whereas reconstitution of SCID-HC with IFN-gamma-/--HC splenocytes did not. The HC-induced oxidant stress was restored in IFN-gamma-/--HC mice reconstituted with WT-HC splenocytes.


CONCLUSIONS
These findings implicate IFN-gamma 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.
Stokes
Karen Y
KY
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 E Kings Highway, Shreveport, La 71130-3932, USA.
Clanton
E Chris
EC
Clements
Kris P
KP
Granger
D Neil
DN
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology*; D005434:Flow Cytometry; D006937:Hypercholesterolemia / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics / Q000502:physiology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology*; D008208:Lymphatic System / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D018384:Oxidative Stress; D013601:T-Lymphocytes / Q000276:immunology
D007371:Interferon-gamma; D002784:Cholesterol