Tissue necrosis factor

Santora, L. C., Krull, I. S., and Grant, K., Characterization of recombinant human monoclonal tissue necrosis factor-alpha antibody using cation-ex-change HPLC and capillary isoelectric focusing, Anal. Biochem., 275, 98,1999. 

We must inteiject an interesting historical sidelight at this point. Despite its reputation, thalidomide made a bit of a comeback in the 1990s (Blakeslee, 1994). Among other properties, thalidomide has been shown to have good anti-inflammatory properties, because it apparently decreases the synthesis and/or release of tissue necrosis factor. 

Thalidomide has significant teratogenic effects in humans, and it also affects the central and peripheral nervous systems through unknown mechanisms. Evidence of a toxic arene oxide metabolite is unsubstantiated. Thalidomide likely inhibits neutrophil chemotaxis and monocyte phagocytosis, inhibits free radical formation, and alters the ratio of helper and suppressor T-cells. Reduced formation of tissue necrosis factor-a may be at least partially responsible for the antiinflammatory effects of thalidomide. 

In some threats, the body s immune response can be overly stimulated, as was the case during the 1918 influenza pandemic. The body can be devastated by the immune response, for example, by a flood of tissue necrosis factor or excessive populations of immnne cells that cause tissue destruction. To counter this, nanoen-gineered bioscavengers may be designed to adsorb the blood-borne toxins and deactivate them or reduce their body burden by enhancing their natural excretion or filtering the nanomaterial-toxin complex from the blood. 

Since osteoblasts and chondrocytes share much of the same environment, the skeletal system, they are exposed to some of the same signaling molecules. However, the same signaling molecules may impact osteoblasts and chondrocytes differently. We will look in depth at some shared cytokines and growth factors such as TGF-(il, lGF-1, BMP-2, BMP-7, tissue necrosis factor (TNF)-a, and interleukin (IL)-i. 

Tumor necrosis factor alpha (TNFa) is a negative regulator of FATP expression and downregulates FATP mRNA and protein levels in several tissues. 

Ketteihut, I.C. Goldberg, A.L (1988). Tumor necrosis factor can induce fever in rats without activating protein breakdown in muscle or lipolysis in adipose tissue. J. Clin. Invest. 81, 1384-1389. 

Mammalian cell suspension cultures are the preferred choice for large-scale recombinant protein production in stirred-tank bioreactors. The most widely used systems are Chinese hamster ovary (CHO) cells and the murine myeloma fines NSO and SP2/0. In half of the biological license approvals from 1996-2000, CHO cells were used for the production of monoclonal antibodies and other recombinant glycosylated proteins, including tPA (tissue plasminogen activator) and an IgGl fusion with the tumor necrosis factor (TNF) receptor, the latter marketed as Enbrel [7]. 

IL-3 also has effects on mature cells. Those reported include the enhancement of the cytotoxicity of macrophages, stimulation of the proliferation of tissue-derived mast cells and (in the presence of endotoxin) the stimulation of the tumouricidal activity of monocytes, possibly via enhanced production of tumour necrosis factor (TNF). However, there are no reported effects of IL-3 on mature neutrophil function. 

Odgren, P.R., Kim, N., McKay, C.A., Mason-Savas, A., Choi, Y., Marks, S.C. Jr. (2003) The Role of RANKL (TRANCE/TNFSFll), a Tumor Necrosis Factor Family Member, in Skeletal Development Effects of Gene Knockout and Transgenic Rescue. Connective Tissue Research 44 Suppl 1, 264-271. 

An interesting additional point is that during trauma the cytokine, tumour necrosis factor, results in a decrease in lipase activity in adipose and other tissues, so that there is an increase in the level of VLDL and chylomicrons in the blood. The significance of this is unclear but it may be that pathogens in the blood are adsorbed onto the emulsion of VLDL or chylomicrons which reduces the risk of adsorption of the pathogen onto the surface of a cell, which is necessary for the pathogen to enter the ceU. This localisation also aids attack by antibodies (Chapter 17). 

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