Interferon-γ elicits arteriosclerosis in the absence of leukocytes

被引:323
作者
Tellides, G
Tereb, DA
Kirkiles-Smith, NC
Kim, RW
Wilson, JH
Schechner, JS
Lorber, MI
Pober, JS
机构
[1] Yale Univ, Sch Med, Boyer Ctr Mol Med, Interdepartmental Program Vasc Biol & Transplanta, New Haven, CT 06510 USA
[2] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA
[3] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA
[4] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA
[5] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06510 USA
关键词
D O I
10.1038/35003221
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Atherosclerosis and post-transplant graft arteriosclerosis are both characterized by expansion of the arterial intima as a result of the infiltration of mononuclear leukocytes, the proliferation of vascular smooth muscle cells (VSMCs) and the accumulation of extracellular matrix(1-3). They are also associated with the presence of the immunomodulatory cytokine interferon-gamma (IFN-gamma)(2,3). Moreover, in mouse models of atheroma formation or allogeneic transplantation, the serological neutralization(4) or genetic absence(5-8) of IFN-gamma markedly reduces the extent of intimal expansion. However, other studies have found that exogenous IFN-gamma inhibits Cultured VSMC proliferation(9-14) and matrix synthesis(15), and reduces intimal expansion in response to mechanical injury(16-18). This discrepancy is generally explained by the idea that IFN-gamma either directly activates macrophages, or, by increasing antigen presentation, indirectly activates T cells within the lesions of atherosclerosis and graft arteriosclerosis. These activated leukocytes are thought to express the VSMC-activating cytokines(1-3) and cell-surface molecules(19) that cause the observed arteriosclerotic responses. Here we have inserted pig and human arteries into the aorta of immunodeficient immunodeficient mice, and we show that IFN-gamma can induce arteriosclerotic changes in the absence of detectable immunocytes by acting on VSMCs to potentiate growth-factor-induced mitogenesis.
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页码:207 / 211
页数:5
相关论文
共 30 条
[1]   CYTOKINES AND GROWTH-FACTORS POSITIVELY AND NEGATIVELY REGULATE INTERSTITIAL COLLAGEN GENE-EXPRESSION IN HUMAN VASCULAR SMOOTH-MUSCLE CELLS [J].
AMENTO, EP ;
EHSANI, N ;
PALMER, H ;
LIBBY, P .
ARTERIOSCLEROSIS AND THROMBOSIS, 1991, 11 (05) :1223-1230
[2]   DEREGULATED EXPRESSION OF THE C-MYC ONCOGENE ABOLISHES INHIBITION OF PROLIFERATION OF RAT VASCULAR SMOOTH-MUSCLE CELLS BY SERUM REDUCTION, INTERFERON-GAMMA, HEPARIN, AND CYCLIC-NUCLEOTIDE ANALOGS AND INDUCES APOPTOSIS [J].
BENNETT, MR ;
EVAN, GI ;
NEWBY, AC .
CIRCULATION RESEARCH, 1994, 74 (03) :525-536
[3]  
BRINCKERHOFF CE, 1985, J IMMUNOL, V134, P3142
[4]  
Castronuovo J J Jr, 1995, Cardiovasc Surg, V3, P463, DOI 10.1016/0967-2109(95)94442-Y
[5]   The unique role of interferon-gamma in the regulation of MHC expression on arterial endothelium [J].
Goes, N ;
Urmson, J ;
Hobart, M ;
Halloran, PF .
TRANSPLANTATION, 1996, 62 (12) :1889-1894
[6]   LYMPHOKINE DEPENDENCE OF INVIVO EXPRESSION OF MHC CLASS-II ANTIGENS BY ENDOTHELIUM [J].
GROENEWEGEN, G ;
BUURMAN, WA ;
VANDERLINDEN, CJ .
NATURE, 1985, 316 (6026) :361-363
[7]   IFN-gamma potentiates atherosclerosis in apoE knock-out mice [J].
Gupta, S ;
Pablo, AM ;
Jiang, XC ;
Wang, N ;
Tall, AR ;
Schindler, C .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (11) :2752-2761
[8]   IMMUNE-MECHANISMS IN ATHEROSCLEROSIS [J].
HANSSON, GK ;
JONASSON, L ;
SEIFERT, PS ;
STEMME, S .
ARTERIOSCLEROSIS, 1989, 9 (05) :567-578
[9]   LYMPHOCYTES-T INHIBIT THE VASCULAR-RESPONSE TO INJURY [J].
HANSSON, GK ;
HOLM, J ;
HOLM, S ;
FOTEV, Z ;
HEDRICH, HJ ;
FINGERLE, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (23) :10530-10534
[10]   INTERFERON-GAMMA INHIBITS ARTERIAL-STENOSIS AFTER INJURY [J].
HANSSON, GK ;
HOLM, J .
CIRCULATION, 1991, 84 (03) :1266-1272