Role of nonspecific cytotoxic cells in the induction of programmed cell death of pathogenic protozoans: Participation of the Fas ligand-Fas receptor system

被引:47
作者
Jaso-Friedmann, L [1 ]
Leary, JH [1 ]
Evans, DL [1 ]
机构
[1] Univ Georgia, Coll Vet Med, Dept Med Microbiol & Parasitol, Athens, GA 30602 USA
关键词
Tetrahymena; nonspecific cytotoxic cells; Fas ligand; Fas receptor; apoptosis; programmed cell death; pathogenic protozoan parasite;
D O I
10.1006/expr.2000.4561
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
Numerous different species of parasites and pathogenic microorganisms produce programmed cell death (PCD) and apoptosis in eukaryotic targets. However, only a few studies have demonstrated that effector cells, cytokines, growth factors, or soluble apoptosis-inducing factors are capable of initiating apoptosis in protozoan parasites. Certain Tetrahymena spp. in teleosts are opportunistic pathogens. In me present study these pathogenic protozoans were developed as a model system to describe the potential role of the Fas ligand (Fast)-Fas receptor (FasR) system as a means of innate immunity in teleosts. Nonspecific cytotoxic cells (NCC) constitutively express soluble Fast (sFasL). Binding of the antigen receptor (i.e., NCCRP-1) on NCC to target cells caused the release of sFasL into the: milieu. The presence of functional sFasL in these supernatants was determined by Western blot analysis and by demonstrating the lysis of FasR(+) HL-60 but not IM-9 (FasR(-)) targets. Soluble Fast containing supernatants generated by tumor cell-activated NCC also produced a reduction in 2 N DNA (i.e., DNA hypoploidy) of T. furgasoni. The induction of DNA hypoploidy by NCC supernatants could be neutralized by adsorption of the supernatants with anti-Fast antibody (but not with an isotype control). Experiments were next done to determine the expression of FasR on Tetrahymena and study the effects of anti-FasR monoclonal crosslinkage and treatment with soluble human recombinant Fast (huFasL) on initiation of PCD in Tetrahymena. Cell cycle analysis revealed that both crosslinkage and soluble huFasL binding to Tetrahymena produced DNA hypoploidy. The reduction in diploid DNA was confirmed by observing oligonucleosome fragmentation (DNA laddering) following anti-FasR treatment. Additional evidence for FasR expression on Tetrahymena was obtained using fluorescence microscopy and flow cytometry. Both methods showed that all Tetrahymena examined (three species consisting of four isolates) expressed membrane FasR. These studies demonstrated the potential of the FasL-FasR system in teleosts for initiation of antiparasite innate immunity. Effector NCC may initiate PCD of Tetrahymena that express a FasR-like protein. Induction of apoptosis may be a major mechanism of homeostatic control of protozoan parasite infestations/infections. (C) 2000 Academic Press.
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页码:75 / 88
页数:14
相关论文
共 61 条
[1]   APOPTOSIS AS A MECHANISM OF CYTOLYSIS OF TUMOR-CELLS BY A PATHOGENIC FREE-LIVING AMEBA [J].
ALIZADEH, H ;
PIDHERNEY, MS ;
MCCULLEY, JP ;
NIEDERKORN, JY .
INFECTION AND IMMUNITY, 1994, 62 (04) :1298-1303
[2]  
AMEISEN JC, 1995, CELL DEATH DIFFER, V2, P285
[3]   FAS-MEDIATED CYTOTOXICITY BY FRESHLY ISOLATED NATURAL-KILLER-CELLS [J].
ARASE, H ;
ARASE, N ;
SAITO, T .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (03) :1235-1238
[4]   Apoptosis in parasites and parasite-induced apoptosis in the host immune system: a new approach to parasitic diseases [J].
Barcinski, MA ;
DosReis, GA .
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, 1999, 32 (04) :395-401
[5]   Activation-induced programmed cell death of nonspecific cytotoxic cells and inhibition by apoptosis regulatory factors [J].
Bishop, GR ;
Jaso-Friedmann, L ;
Evans, DL .
CELLULAR IMMUNOLOGY, 2000, 199 (02) :126-137
[6]  
BISHOP GR, 2000, UNPUB MECH NONSPECIF
[7]  
Brown SB, 1999, J IMMUNOL, V162, P480
[8]   STABILITY OF DIVISION-RELATED PROTEIN AND NUCLEIC ACID FRACTIONS IN SYNCHRONIZED TETRAHYMENA [J].
BYFIELD, JE ;
SCHERBAUM, OH .
JOURNAL OF CELLULAR PHYSIOLOGY, 1967, 70 (03) :265-+
[9]   PERTUSSIS-TOXIN-SENSITIVE GTP-BINDING PROTEINS REGULATE ACTIVATION-INDUCED APOPTOTIC CELL-DEATH OF HUMAN NATURAL-KILLER-CELLS [J].
CARRACEDO, J ;
RAMIREZ, R ;
MARCHETTI, P ;
PINTADO, OC ;
BAIXERAS, E ;
MARTINEZ, C ;
KROEMER, G .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (11) :3094-3099
[10]   Staurosporine-induced cell death in Tetrahymena thermophila has mixed characteristics of both apoptotic and autophagic degeneration [J].
Christensen, ST ;
Chemnitz, J ;
Straarup, EM ;
Kristiansen, K ;
Wheatley, DN ;
Rasmussen, L .
CELL BIOLOGY INTERNATIONAL, 1998, 22 (7-8) :591-598