Cytotoxicity in macrophages

Szabd C, Zingarelli B, O Connor M et al. DNA strand breakage, activation of poly-ADP tibosyl synthetase, and cellular energy depletion are involved in the cytotoxicity in macrophages and smooth muscle cells exposed to peroxynitrite. Proc Natl Acad Sd USA 1996 93 1753-1758. 

When induced in macrophages, iNOS produces large amounts of NO which represents a major cytotoxic principle of those cells. Due to its affinity to protein-bound iron, NO can inhibit a number of key enzymes that contain iron in their catalytic centers. These include ribonucleotide reductase (rate-limiting in DNA replication), iron-sulfur cluster-dependent enzymes (complex I and II) involved in mitochondrial electron transport and cis-aconitase in the citric acid cycle. In addition, higher concentrations of NO,... 

Montavani, A., et. al., Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on macrophage and natural killer cell-mediated cytotoxicity in mice, Biomedicine, 32, 200, 1980. 

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. 

NO generated in the immune system does not operate through GC. Instead, NO appears to act directly as a cytotoxic molecule or as some other reactive product such as ONOO (peroxynitrite). During the immune oxidative burst in macrophage cells, reactive oxygen intermediates. 

In vitro assay of a number of respirable talc specimens of high purity demonstrated a modest but consistent cytotoxicity to macrophages the investigators conclude that the talcs would be expected to be slightly fibro-genic in vivo. ... 

Jones, 1971), and it is now known that these cytotoxic activated macrophages (CAMs) can be formed in vitro from macrophages by a combination of two signals, usually interferon-y and lipopolysaccharide (a major component of the cell wall of gram-negative bacteria). 

Drapier, J. C., and Hibbs, J. B., Jr. (1986). Murine cytotoxic activated macrophages inhibit aconitase in tumor cells. Inhibition involves the iron-sulfur prosthetic group and is reversible. J. Clin. Invest. 78, 790-797. 

Antibacterial activity in serum of the 3,5-diamino translation inhibitor, compound 511 was determined against Escherichia coli and Pseudomonas aeruginosa (08BML3369). Antileishmanial and cytotoxicity toward macrophages of 2,3-dihydro-5H-pyrido[l,2,3-de][l,4]benzoxazin-5-one was measured (09EJM845). 

Our SAR study of paclitaxel analogues on their ability to activate macrophage, inducing the production of NO and TNF, has revealed stark differences in the structural requirements for cytotoxicity vs. macrophage activation. The results warrant a great deal of further study on the possible alternative or auxiliary mechanism of action for paclitaxel and taxoids, which might lead to the discovery of a new series of taxoid anticancer agents with unique mechanism of action. 

Aniano, K. and Yoon, J. W. (1990). Studies on autoimmunity for initiation of beta-cell destruction. V. Decrease of macrophage-dependent T lymphocytes and natural killer cytotoxicity in silica-treated BB rats.Diabetes 39, 590-596. 

Type II, or cytotoxic immune, responses can be complement-independent or complement-dependent in nature. In the former case, IgG antibodies bind to antigens attached to the surface of normal cells (e.g., erythrocytes, platelets, etc.). Cytotoxic cells (macrophages, neutrophils, and eosinophils) then attach to the crystallizable fragment (Fc) portion of the antigen, release cytotoxic granules, and lyse the cell. 

Cytotoxic activated macrophages (CAMs) macrophages that have been treated either in vivo or in vitro by exposme to a combination of bacterial products (such as endotoxin) plus cytokines (particularly interferon-y), rendering them able to kill or damage abnormal cells (cancerous or infected with pathogenic microbe or vims) or pathogen. An important component of the CAMs armamature for this cytotoxic mechanism is production of -NO... 

What are the specific intracellular derangements that occur in target cells (specifically, tumor cells) in response to activated macrophages In 1980, Krahenbuhl studied the in vitro (in culture) effects of murine cytotoxic activated macrophages (CAMS, produced by injection of killed C. parvum) on EMT-... 

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