Liver and circulating NK1.1+CD3- cells are increased in infection with attenuated Salmonella typhimurium and are associated with reduced tumor in murine liver cancer

被引:20
作者
Feltis, BA
Miller, JS
Sahar, DA
Kim, AS
Saltzman, DA
Leonard, AS
Wells, CL
Sielaff, TD
机构
[1] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA
[3] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA
关键词
D O I
10.1006/jsre.2002.6428
中图分类号
R61 [外科手术学];
学科分类号
摘要
An attenuated (DeltacyA, Deltacrp) strain of Salmonella typhimurium (chi4550) containing a gene for human IL-2 (chi4550pIL2) reduces hepatic tumor burden when orally inoculated into mice with liver cancer; however, wild-type S. typhimurium is also associated with cancer regression. Therefore, experiments were designed to clarify the invasiveness and the anti-tumor properties of three strains of S. typhimurium. S. typhimurium chi4550pIL2, chi4550, or wild type (WT) was incubated with mature Caco-2 and HT-29 enterocytes, and S. typhimurium internalization was assessed. For infectivity experiments, mice were orally inoculated with saline or 10(9) S. typhimurium chi4550pIL2, chi4550, or WT; 48 h later mice were sacrificed for analysis of cecal bacteria and S. typhimurium translocation to mesenteric lymph nodes. For experiments involving tumor implantation, four groups were studied: saline control, tumor alone, chi4550pIL2+tumor, and chi4550+tumor. Mice were orally inoculated with saline or S. typhimurium and underwent laparotomy 24 h later with 5 X 10(4) MCA38 murine adenocarcinoma cells injected into the spleen. On day 14, liver tumors were counted and peripheral blood and hepatic lymphocyte populations were analyzed by FACScan. Attenuated S. typhimurium exhibited decreased internalization by cultured enterocytes and decreased infectivity after oral inoculation. Mice treated with chi4550pIL2 or chi4550 had fewer liver tumors and increased populations of hepatic and circulating NK1.1(+)CD3(-) lymphocytes compared to mice treated with saline (P < 0.01). These data suggest that attenuated S. typhimurium may have an application as an anti-tumor agent. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:101 / 107
页数:7
相关论文
共 43 条
[1]  
ADAMS DO, 1981, J IMMUNOL, V126, P981
[2]  
[Anonymous], 1989, FUNCTIONAL EPITHELIA
[3]   INHIBITION OF MACROPHAGE PHAGOSOME-LYSOSOME FUSION BY SALMONELLA-TYPHIMURIUM [J].
BUCHMEIER, NA ;
HEFFRON, F .
INFECTION AND IMMUNITY, 1991, 59 (07) :2232-2238
[4]  
CAREY R. W., 1967, EUR J CANCER, V3, P37, DOI 10.1016/0014-2964(67)90060-6
[5]  
Castro A, 1998, EUR J IMMUNOL, V28, P488, DOI 10.1002/(SICI)1521-4141(199802)28:02<488::AID-IMMU488>3.0.CO
[6]  
2-R
[7]  
Coley W.B., 1893, AM J MED SCI, V105, P487, DOI DOI 10.1097/00000441-189305000-00001
[8]  
CORBETT TH, 1975, CANCER RES, V35, P2434
[9]   SALMONELLA-TYPHIMURIUM DELETION MUTANTS LACKING ADENYLATE-CYCLASE AND CYCLIC-AMP RECEPTOR PROTEIN ARE AVIRULENT AND IMMUNOGENIC [J].
CURTISS, R ;
KELLY, SM .
INFECTION AND IMMUNITY, 1987, 55 (12) :3035-3043
[10]   Oral somatic transgene vaccination using attenuated S-typhimurium [J].
Darji, A ;
Guzman, CA ;
Gerstel, B ;
Wachholz, P ;
Timmis, KN ;
Wehland, J ;
Chakraborty, T ;
Weiss, S .
CELL, 1997, 91 (06) :765-775