A RAT CYTOMEGALOVIRUS-INFECTION MODEL AS A TOOL FOR IMMUNOTOXICITY TESTING

被引：32

作者：

GARSSEN, J ^{[1
]}

VANDERVLIET, H ^{[1
]}

DEKLERK, A ^{[1
]}

GOETTSCH, W ^{[1
]}

DORMANS, JAMA ^{[1
]}

BRUGGEMAN, CA ^{[1
]}

OSTERHAUS, AME ^{[1
]}

VANLOVEREN, H ^{[1
]}

机构：

[1] UNIV LIMBURG,6200 MD MAASTRICHT,NETHERLANDS

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION | 1995年 / 292卷 / 3-4期

关键词：

CYTOMEGALOVIRUS; IMMUNOTOXICITY TESTING; ULTRAVIOLET LIGHT; BIS(TRI-N-BUTYLTIN)OXIDE;

D O I：

10.1016/0926-6917(95)90026-8

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A rat cytomegalovirus infection model for use in immunotoxicity testing has been developed. In resistance against viruses, natural killer cells and cytotoxic T-cells play an important role. Therefore, this model complements other rat host resistance models for immunotoxicity testing, i.e. existing bacterial and parasitic infection models in which cytotoxic T-cells and natural killer cells play a minor role. Host resistance against cytomegalovirus infections in the rat was determined by titrating infectious virus levels in organs after cytomegalovirus infection in an in vitro infectivity test denoted as the Plaque Forming Unit (PFU) Test, In this test, homogenates of different organs were investigated for infectious virus titers on rat embryonic cell monolayers. We demonstrated that in the salivary gland, the major target organ for rat cytomegalovirus, virus was detectable from 8 days onward after intraperitoneal infection. To show that this model is suitable for the detection of immunotoxicity four different methods for immunosuppression were investigated: 1. gamma-irradiation, 2. congenitally athymic rats, 3. chemically induced immunosuppression, 4. ultraviolet-B (UVB) irradiation. Rat cytomegalovirus titers in the salivary glands of irradiated (500 rad 1 day prior to infection) or congenitally athymic rats were significantly increased as compared to non-irradiated rats and euthymic control rats respectively. In TOX-Wistar rats, given 20 or 80 mg bis(tri-n-butyltin)oxide (TBTO) per kg food beginning 6 weeks before cytomegalovirus infection, a regimen known to have immunotoxic effects, cytomegalovirus titers in the salivary glands were significantly increased as compared to non-TBTO-treated cytomegalovirus infected rats. Exposure to a suberythemal doses of UVB, which is known to induce immunotoxic effects, induced a significant increase in cytomegalovirus titers in the salivary gland as compared to non-UVB-exposed rats. Therefore it is concluded that this infection model is suitable for the assessment of immunotoxic effects induced by environmental components.

引用

页码：223 / 231

页数：9

共 38 条

[1]

Bruggeman, Meijer, Dormans, Debie, Grauls, Van Boven, Isolation of a cytomegalovirus-like agent from wild rats, Arch. Virol., 73, (1982)

[2]

Bruggeman, Debie, Grauls, Majoor, Van Boven, Infection of laboratory rats with a new cytomegalo-like virus, Arch. Virol., 76, (1983)

[3]

Bruggeman, Meijer, Bosman, Van Boven, Biology of rat cytomegalovirus, Intervirology, 24, (1985)

[4]

Bruning, Bruggeman, Van Boven, Van Breda Vriesman, Passive transfer of cytomegalovirus by cardiac and renal organ transplantation in a rat model, Transplantation, 41, (1986)

[5]

Bukowski, Woda, Welsh, Pathogenesis of murine cytomegalovirus infection in natural killer cell-depleted mice, J. Virol., 52, (1984)

[6]

De Jong, Steerenberg, Ursem, Osterhaus, Vos, Ruitenberg, The athymic nude rat. III. Natural cell-mediated cytotoxicity, Clin. Immunol. Immunopathol., 17, (1980)

[7]

Garssen, Goettsch, Deyns, Van Der Vliet, Pierik, De Gruyl, Van Loveren, UV-B suppressess resistance against systemic (not-skin- related) infections, J. Invest. Dermatol., 160, 9, (1993)

[8]

Goettsch, Garssen, De Gruyl, Van Loveren, UV-B and the immune system. A review with special emphasis on T cell mediated immunity, Thymus, 21, (1993)

[9]

Goettsch, Garssen, Deyns, De Gruyl, Van Loveren, UVB exposure impairs resistance to infections with Trichinella spiralis, Environ. Health Perspect., 102, (1994)

[10]

Hodgkin, Scalzo, Swaminathan, Price, Shellam, Murine cytomegalovirus binds reversibly to mouse embryo fibroblasts: implications for quantification and explanation of centrifugal enhancement, J. Virol. Meth., 22, (1988)

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