TY - JOUR
T1 - Studies of connective tissue mast cell-mediated cytotoxicity
AU - Tharp, Michael D.
AU - Kasper, Candace
AU - Thiele, Dwain L
AU - Charley, Michael R.
AU - Kennerly, Donald A.
AU - Sullivan, Timothy J.
PY - 1989/9
Y1 - 1989/9
N2 - Although mast cells have been implicated in mediating anti-tumor activity, the kinetics, mechanism(s), and suspectibility of different tumors to mast cell-mediated cytotoxicity have not been defined. Rat connective tissue mast cells (CTMC) of ≥99% purity were investigated in vitro and found to express maximal spontaneous cytotoxicity against the mouse fibrosarcoma cell line WEHI-164 (56.0% ± 2.1 SEM), the ultraviolet B (UVB)-induced, cutaneous fibrosarcoma 5C25 (34.7% ± 3.4 SEM), and the human renal cell tumor Currie (26.8% ± 2.0 SEM) at an effector to target (E:T) ratio of 80: 1. Kinetic studies of CTMC-mediated cytotoxicity demonstrated significant detectable lysis against these tumors within 8 h, which was maximal by 16 h. Binding experiments showed that CTMC formed conjugates with all three lytic-sensitive targets; however, CTMC also attached to the lytic-resistant target YAC-1, indicating that conjugate formation alone is not sufficient for mast cell-mediated cytotoxicity. At two different concentrations, mast cell granules (MCG) lysed WEHI-164 (36.5% ± 6.8 SEM) and 5C25 (34.4% ± 6.9 SEM), but were only slightly cytotoxic (5.7% ± 2.9 SEM) against Currie. A potential role for tumor necrosis factor-alpha (TNF-α) in CTMC-mediated cytotoxicity also was investigated. Polyclonal antibodies to TNF-α greatly reduced CTMC and TNF-mediated lysis of WEHI-164, but only partially inhibited CTMC killing of the slightly TNF-sensitive 5C25 tumors, and had no effect on CTMC cytolysis of Currie. Thus, this study demonstrates that CTMC mediate cytotoxicity in vitro by both TNF-associated and TNF-independent mechanisms. We conclude that CTMC are capable of mediating antitumor activity and that this effect may be important for tumor surveillance in the skin and other sites.
AB - Although mast cells have been implicated in mediating anti-tumor activity, the kinetics, mechanism(s), and suspectibility of different tumors to mast cell-mediated cytotoxicity have not been defined. Rat connective tissue mast cells (CTMC) of ≥99% purity were investigated in vitro and found to express maximal spontaneous cytotoxicity against the mouse fibrosarcoma cell line WEHI-164 (56.0% ± 2.1 SEM), the ultraviolet B (UVB)-induced, cutaneous fibrosarcoma 5C25 (34.7% ± 3.4 SEM), and the human renal cell tumor Currie (26.8% ± 2.0 SEM) at an effector to target (E:T) ratio of 80: 1. Kinetic studies of CTMC-mediated cytotoxicity demonstrated significant detectable lysis against these tumors within 8 h, which was maximal by 16 h. Binding experiments showed that CTMC formed conjugates with all three lytic-sensitive targets; however, CTMC also attached to the lytic-resistant target YAC-1, indicating that conjugate formation alone is not sufficient for mast cell-mediated cytotoxicity. At two different concentrations, mast cell granules (MCG) lysed WEHI-164 (36.5% ± 6.8 SEM) and 5C25 (34.4% ± 6.9 SEM), but were only slightly cytotoxic (5.7% ± 2.9 SEM) against Currie. A potential role for tumor necrosis factor-alpha (TNF-α) in CTMC-mediated cytotoxicity also was investigated. Polyclonal antibodies to TNF-α greatly reduced CTMC and TNF-mediated lysis of WEHI-164, but only partially inhibited CTMC killing of the slightly TNF-sensitive 5C25 tumors, and had no effect on CTMC cytolysis of Currie. Thus, this study demonstrates that CTMC mediate cytotoxicity in vitro by both TNF-associated and TNF-independent mechanisms. We conclude that CTMC are capable of mediating antitumor activity and that this effect may be important for tumor surveillance in the skin and other sites.
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U2 - 10.1016/0022-202X(89)90070-5
DO - 10.1016/0022-202X(89)90070-5
M3 - Article
C2 - 2768840
AN - SCOPUS:0024416765
SN - 0022-202X
VL - 93
SP - 423
EP - 428
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 3
ER -