Mechanisms of nonspecific cytotoxic cell regulation of apoptosis: cytokine-like activity of Fas ligand

Effect of PHA and LPS on the Activity of Nonspecific Cytotoxic Cells and Macrophages of Rainbow Trout (Oncorhynchus mykiss)

“…1 shows that PHA did not signifi cantly increased cytotoxic activity by NCCs after 24 h, the increase in activity is apparent, becoming signifi cant at the next sampling time. Considering that the cytotoxic activity increase is maintained in the presence of EGTA (condition in which perforins/granzymes should not be operative) and since HL-60 cells have FasR and therefore are targets to lysis by the FasL-FasR system (Bishop et al 2002), our result support the presence of the FasR-FasL system in salmonids but additional immunological and molecular studies are required to confi rm it. This result agrees with that reported by Kurata et al (2011) showing that 10 μg/ml of PHA signifi cantly increased FasL transcription in the Japanese fl ounder (Paralichthys olivaceus).…”

“…Among the cellular components of fi sh innate immunity we can include cytotoxic cells, functionally homologous to natural killer cells (NK) of mammals, called nonspecifi c cytotoxic cells (NCCs) (Bishop et al 2002;Ristow et al 2000;Evans & Jaso-Friedmann 1992). Since their main function is to eliminate cells infected with intracellular pathogens (bacteria and virus) and also tumor cells, lysing them or inducing them to undergo apoptosis, NCCs play an important role in fi sh immunity (Ellis 2001;Ristow et al 2000;Hogan et al 1996;Evans & Jaso-Friedmann 1992).…”

“…Perforins polymerize in the membrane of target cells, depending on Calcium, producing a pore leading to the lysis of the target cell and granzymes, whose entry is facilitated by perforins, induce their apoptosis. A second cytotoxic mechanism, independent of Calcium, leading to the apoptosis of infected or altered cells is mediated by the Fas receptor-Fas ligand (FasR-FasL) system, involving the interaction of Fas-L (located in the membrane of cytotoxic cells) with the Fas-R (located in the membrane of target cells) (Kaur et al 2004;Cuesta et al 2003;Bishop et al 2002) making target cells lacking FasR resistant to this mechanism. Using Calcium chelating agents, such as EGTA, it is possible to avoid perforins/granzymes mediated target cells lysis, making it possible to evaluate in vitro the activity of one or both of these mechanisms (Duke 2000).…”

Fighting Virus and Parasites with Fish Cytotoxic Cells

“…In the last decade, fish perforin (Athanasopoulou et al, 2009;Hwang et al, 2004;Toda et al, 2011a) and granzyme (Huang et al, 2010;Praveen et al, 2004Praveen et al, , 2006Wernersson et al, 2006) sequences have been obtained but their gene expression or function has been scarcely related to the innate cytotoxic activity (Ordás et al, 2011;Praveen et al, 2006). The granule-independent killing mechanism has also been identified in fish NCCs by the use of commercial antibodies or functional studies (Ca-chelators) leading to the identification of the Fas/FasL system in fish NCCs (Bishop et al, 2002;Cuesta et al, 2003a;Evans et al, 200, 2001;Jaso-Friedmann et al, 2000;Kaur et al, 2004;Long et al, 2004). After the delivery of the lethal hit, the killing of the target cells occurs by two conserved pathways: necrosis and apoptosis (Cuesta et al, 1999;Meseguer et al, 1994Meseguer et al, , 1996Mulero et al, 1994).…”

“…Fish NCC activity has been shown to be modulated by several chemicals, cytokines, environmental contaminants, stress factors, immunostimulants, etc. First studies dealt with the NCC inhibition by blocking the binding to target in order to characterize the role of NCCRP-1, or inhibiting the killing mechanisms in order to evaluate the perforin-or Fas/FasL-mediated lytic pathway (Bishop et al, 2002;Carlson et al, 1985;Evans et al, 1988Hogan et al, 1999;Iwanowicz et al, 2004;Jaso-Friedmann et al, 1988Kaur et al, 2004;Shen et al, 2002). Further studies demonstrated that catfish NCC activity is increased by leucocyte treatment with ionophore A23187, A23187 plus phorbol myristate acetate (PMA) or vanadate but no with PMA alone or poly I:C (a mimic for viral infections) (Evans et al, 1984b(Evans et al, , 1990(Evans et al, , 1998b.…”