Tumor necrosis factor (TNFα) is present in elevated levels in peritoneal fluid from infertile women with endometriosis. The effect of TNFα on human sperm motility in vitro was evaluated utilizing peritoneal fluid from infertile women with minimal endometriosis containing 0, 100, 400, or 800 U of TNFα/ml as well as similar concentrations of recombinant human TNFα. No reduction in progressive and total motility was found at recombinant TNFα concentrations of 100 U ml. However, 500 and 1000 U of recombinant TNFα/ml caused a significant reduction in progressive and total sperm motility after 4 and 21 hours of incubation when compared with controls. Similarly, peritoneal fluid containing 100 U of TNFα/ml did not significantly reduce progressive and total sperm motility after either 4 or 21 hours of incubation; but peritoneal fluid containing 400 U of TNFα/ml reduced progressive sperm motility after 4 and 21 hours and total sperm motility after 21 hours of incubation. Peritoneal fluid with a TNFα concentration of 800 U/ml caused a significant reduction in both progressive and total sperm motility after 4 and 21 hours when compared with controls of TNFα‐negative peritoneal fluid. The addition of polyclonal rabbit anti‐TNFα antibody or 30‐min heat inactivation at 56 C of TNFα‐positive peritoneal fluid reversed the inhibitory effect on sperm motility. The ability of TNFα to cause a significant reduction of sperm motility in vitro suggests that this may be a mechanism for the infertility observed in women with minimal endometriosis.
Detailed analysis of the natural killer (NK) activity directed at nontumorigenic cell lines and their transformed tumorigenic derivatives has revealed a paradox. On the one hand, a correlation has been found between the tumorigenic potential of chemically transformed fibroblast cell lines and their sensitivity to NK cells in vitro. Nontransformed cells (N-type cell lines) and cells tumorigenic in normal mice (C-type cell lines) are resistant to NK-mediated lysis. In contrast, cell lines that are tumorigenic in ATxFL mice (these mice are very low in NK activity), but not in normal mice (I-type cell lines) are sensitive to NK-mediated lysis. These findings support the concept that NK activity is involved in host surveillance against tumors. On the other hand, NK-resistant fibroblasts, whether taken directly form animals or derived as tumorigenic or nontumorigenic cell lines, compete with NK-sensitive target cells to inhibit their lysis by NK effectors. Not only are both NK-sensitive and -resistant cells recognized by NK effectors but both receive lytic signals from NK effector cells. Target cell resistance is a result of a protein synthesis-dependent mechanism that prevents lysis such that in the presence of inhibitors of protein synthesis all fibroblasts tested are NK sensitive. Those fibroblasts that are normally sensitive to NK-mediated lysis must be deficient in their ability to produce or respond to this counterlytic mechanism. These findings are in contrast with the general findings when lymphoid cells are studied as NK targets where sensitivity appears to be a result of recognition by NK effectors. Because our findings show that transformed and normal cells express the same recognition determinants, in order for NK activity to play an important in vivo role in tumor surveillance, a mechanism must operate to permit NK effectors to find their targets in vivo. In the absence of a special discrimination mechanism, the killing of NK-sensitive transformants that arise autochronously would be less than optimal as a consequence of competition by the normal, NK-resistant, cells.
It has been proposed that a component of the antitumor potential of the chemotherapeutic agent, cisplatin, resides in the host's ability to respond to cisplatin-treated tumor cells. Here we report that tumor cells that are normally resistant to lysis mediated by naturally occurring cytotoxic cells showed an increased sensitivity to lysis mediated by murine spleen cells or human peripheral blood monocytes and lymphocytes when cisplatin was added at the beginning of the lytic assay. This was shown for the lysis of both murine and human tumor cells. The pretreatment of tumor cells, but not effector cells with cisplatin caused an increase in lysis in the presence of murine spleen cells or human peripheral blood leukocytes, indicating that the effect of cisplatin is to reduce resistance to lysis by these effector cells. The lysis of tumor cells by naturally occurring cytotoxic cells was blocked by antibodies specific for tumor necrosis factor. In addition, the ability of cisplatin to increase lysis was seen with cells that are sensitive to natural cytotoxic cells, but not with cells that are sensitive to natural killer cells. These results suggest that the effector cells that mediate the lysis of these tumor cells in the presence of cisplatin are likely to be natural cytotoxic cells. The ability of cisplatin to increase the lysis of tumor cells by naturally occurring cytotoxic cells indicates that these cells may be a host defense mechanism that contributes to the anticancer potential of cisplatin.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.