Cytotoxic factors

TNF-a is also known as cachectin, macrophage cytotoxic factor, macrophage cytotoxin and necrosin. As some of these names suggest, activated macrophages appear to represent the most significant cellular source of TNF-a, but it is also synthesized by many other cell types (Table 9.5). Producer cells do not store TNF-a, but synthesize it de novo following activation. 

Natural killer cytotoxic factor A-formylkynurenine A-methyl-D-aspartate Nicotinamide mononucleotide Nuclear magnetic resonance Nitric oxide... 

Cytotoxic factors include tumour necrosis factor (TNF) which is similar to interleukin-1. 

The compounds tested showed mitogenic effects,i.e. they stimulated lymphocyte proliferation. Astonishingly, a DIVEMA-DNP conjugate did not induce the production of DNP-specific antibodies. Our results suggest that this is due to the formation of DNP-specific active suppressor cells. Using serum free culture media, we could show for the first time that DIVEMA and derivatives stimulate macrophages to release cytotoxic factors into the supernatant. However, no significant release of lytic enzymes was detected. 

DIVEMA and the derivatives tested failed to stimulate endocytosis by macrophages of iZ5I-PVP and 198/ u (colloidal) higher mol. wt. DIVEMA inhibited pinocytosis. We conclude that the only effect of the compounds tested on macrophages is the release of cytotoxic factors into the supernatant. 

Do DIVEMA derivatives stimulate macrophages in vitro, i.e. do they induce the release of lytic enzymes or cytotoxic factors ... 

Schultz eT"al. (21, 22) found that macrophages of DIVEMA-treated mice iFFibited tumour cell proliferation in vitro this means that DIVEMA activates macrophages. The authors did not find cytotoxic factors in the supernatant of these macrophage cultures. 

Release of cytotoxic factors into the supernatant was tested by adding the supernatant of DIVEMA-treated macrophages to cultures of defined amounts of P815 tumour cells and measuring LDH from lysed tumour cells after 24 hr. of incubation. 

ZZ) this may be due to the fact that these authors used serum-containing culture media. Our results demonstrate that even chemically modified DIVEMA causes - at least in vitro - the same biological effect (release of cytotoxic factors) as DIVEMA itself. This aspect is especially important if one uses DIVEMA as a carrier polymer for antitumour agents hoping to retain immune stimulating properties. 

G19. Granger, G. A., and Williams, T. W. Lymphocyte cytotoxicity in vitro. Activation and release of a cytotoxic factor. Nature (London) 218, 1253-1255 (1968). 

Meerpohl HG, Lohmann-Matthes ML, Fischer H (1976) Studies on the activation of mouse bone-marrow derived macrophages by the macrophage cytotoxicity factor (MCF). Eur J Immunol 6 213-217... 

The first is the antibody-dependent cellular cytotoxicity (ADCC), the mechanism by which the antigen binding site of a therapeutic protein, for example, a mAb or a molecule with a similar structure, binds to its receptors on the target cells and the Fc portion of the antibody binds to FcR on the effector cells, mainly natural killer (NK) cells. As a result the effector cells are activated to release cytotoxic factors, which induce rupture of the membrane of the target cells. ... 

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