Published Online
on April 14, 2003

A more recent version of this article appeared on April 29, 2003

This Article Full Text (PDF) All Versions of this Article: 107/16/2140    most recent 01.CIR.0000062687.80186.A0v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stokes, K. Y. Articles by Granger, D. N. Search for Related Content PubMed PubMed Citation Articles by Stokes, K. Y. Articles by Granger, D. N. Related Collections Risk Factors Oxidant stress Mechanism of atherosclerosis/growth factors

Submitted on November 11, 2002
Accepted on January 21, 2003

Role of Interferon- in Hypercholesterolemia-Induced Leukocyte-Endothelial Cell Adhesion

Karen Y. Stokes BAMod, E. Chris Clanton , Kris P. Clements BA, and D. Neil Granger PhD^*

From the Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, La.

^* To whom correspondence should be addressed. 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

This article has been cited by other articles:

				K. Y. Stokes, L. Calahan, C. M. Hamric, J. M. Russell, and D. N. Granger CD40/CD40L contributes to hypercholesterolemia-induced microvascular inflammation Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H689 - H697. [Abstract] [Full Text] [PDF]

				M. S. Desai, M. M. Mariscalco, A. Tawil, J. G. Vallejo, and C. W. Smith Atherogenic diet-induced hepatitis is partially dependent on murine TLR4 J. Leukoc. Biol., June 1, 2008; 83(6): 1336 - 1344. [Abstract] [Full Text] [PDF]

				R. M. Wolfort, K. Y. Stokes, and D. N. Granger CD4+ T lymphocytes mediate hypercholesterolemia-induced endothelial dysfunction via a NAD(P)H oxidase-dependent mechanism Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2619 - H2626. [Abstract] [Full Text] [PDF]

				K. Y. Stokes, S. Gurwara, and D. N. Granger T-Cell-Derived Interferon-{gamma} Contributes to Arteriolar Dysfunction During Acute Hypercholesterolemia Arterioscler Thromb Vasc Biol, September 1, 2007; 27(9): 1998 - 2004. [Abstract] [Full Text] [PDF]

				C. Anthoni, J. Russell, K. C. Wood, K. Y. Stokes, T. Vowinkel, D. Kirchhofer, and D. N. Granger Tissue factor: a mediator of inflammatory cell recruitment, tissue injury, and thrombus formation in experimental colitis J. Exp. Med., July 9, 2007; 204(7): 1595 - 1601. [Abstract] [Full Text] [PDF]

				Y.-C. Tsai, H.-J. Hsieh, F. Liao, C.-W. Ni, Y.-J. Chao, C.-Y. Hsieh, and D. L. Wang Laminar flow attenuates interferon-induced inflammatory responses in endothelial cells Cardiovasc Res, June 1, 2007; 74(3): 497 - 505. [Abstract] [Full Text] [PDF]

				G. Yilmaz, T. V. Arumugam, K. Y. Stokes, and D. N. Granger Role of T Lymphocytes and Interferon-{gamma} in Ischemic Stroke Circulation, May 2, 2006; 113(17): 2105 - 2112. [Abstract] [Full Text] [PDF]

				R. W. Alexander Leukocyte and Endothelial Angiotensin II Type 1 Receptors and Microvascular Thrombotic and Inflammatory Responses to Hypercholesterolemia Arterioscler Thromb Vasc Biol, February 1, 2006; 26(2): 240 - 241. [Full Text] [PDF]

				T. Petnehazy, K. Y. Stokes, K. C. Wood, J. Russell, and D. N. Granger Role of Blood Cell-Associated AT1 Receptors in the Microvascular Responses to Hypercholesterolemia Arterioscler Thromb Vasc Biol, February 1, 2006; 26(2): 313 - 318. [Abstract] [Full Text] [PDF]

				Q. Tong, E. V. Vassilieva, A. I. Ivanov, Z. Wang, G. T. Brown, C. A. Parkos, and A. Nusrat Interferon-{gamma} Inhibits T84 Epithelial Cell Migration by Redirecting Transcytosis of {beta}1 Integrin from the Migrating Leading Edge J. Immunol., September 15, 2005; 175(6): 4030 - 4038. [Abstract] [Full Text] [PDF]

				K. Y Stokes and D. N. Granger The microcirculation: a motor for the systemic inflammatory response and large vessel disease induced by hypercholesterolaemia? J. Physiol., February 1, 2005; 562(3): 647 - 653. [Abstract] [Full Text] [PDF]

				T. Petnehazy, K. Y. Stokes, J. M. Russell, and D. N. Granger Angiotensin II Type-1 Receptor Antagonism Attenuates the Inflammatory and Thrombogenic Responses to Hypercholesterolemia in Venules Hypertension, February 1, 2005; 45(2): 209 - 215. [Abstract] [Full Text] [PDF]

				T. V. Arumugam, J. W. Salter, J. H. Chidlow, C. M. Ballantyne, C. G. Kevil, and D. N. Granger Contributions of LFA-1 and Mac-1 to brain injury and microvascular dysfunction induced by transient middle cerebral artery occlusion Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2555 - H2560. [Abstract] [Full Text] [PDF]

				K. Y. Stokes, E. C. Clanton, J. L. Gehrig, and D. N. Granger Role of interleukin 12 in hypercholesterolemia-induced inflammation Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2623 - H2629. [Abstract] [Full Text] [PDF]