Granulocyte necrosis

Therefore, it is reasonable to hypothesize that granulocyte necrosis at inflamed sites can be regarded as a deleterious and undesirable mode of clearance which, by contrast with apoptosis, is likely to fevour persistence of inflammatory tissue injury rather than resolution of inflammation. 

TUMOR NECROSIS FACTOR ALPHA STIMULATES THE GROWTH OF THE CLONOGENIC CELLS OF ACUTE MYELOBLASTIC LEUKEMIA IN SYNERGY WITH GRANULOCYTE / MACROPHAGE COLONY -STIMULATING FACTOR... 

Wing, E J. et al., Recombinant human granulocyte/macrophage colony-stimulating factor enhances monocyte cytotoxicity and secretion of tumor necrosis factor alpha and interferon in cancer patients, Blood, 73, 643, 1989. 

Cicco, N. A., Lindemann, A., Content, J., Vandenbussche, P., Lubbert, M., Gauss, J., Mertelsmann, R., Herrmann, F. (1990). Inducible production of Interleukin-6 by human polymorphonuclear neutrophils Role of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha. Blood 75,2049-52. 

McColl, S. R., Paquin, R., Menard, C., Beaulieu, A. D. (1992). Human neutrophils produce high levels of the interleukin 1 receptor antagonist in response to granulocyte/ macrophage colony-stimulating factor and tumor necrosis factor a. J. Exp. Med. 176, 593-8. 

Alvaro-Gracia, J. M., Zvaifler, N. J., Brown, C. B., Kaushansky, K., Firestein, G. S. (1991). Cytokines in chronic inflammatory arthritis VI. Analysis of the synovial cells involved in granulocyte-macrophage colony-stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and tumor necrosis factor-a J. Immunol 146,3365-71. 

Hearts obtained at autopsy in consecutive AIDS cases (PI), leukocytic phenotype, and presence of viral antigens were investigated in paraffin-embedded and frozen myocardial sections by different monoclonal antibodies. The total frequency of local lymphocytic infiltrates with and without myocell necrosis was 26 and 32%, respectively. In control cases (HIV negative), these infiltrates are absent. In AIDS patients, the number of infiltrative foci per section, their wall distribution (subendocardial, middle layer, subepicardial), number of leukocytes per focus, and cell phenotype (prevalence of CD8 +, absence of B cells and granulocytes) were similar in cases with and without myocell necrosis. 

Figure 3 Cytokine secretion in immunopotentiating reconstituted influenza viro-somes (IRIV)-stimulated peripheral blood mononuclear cells (PBMC). PBMC from a healthy donor were cultured in the absence of stimuli (Neg) or in the presence of IRIV (V, 1 50 diluted) or control liposomes (L, 1 50 diluted). On days 1, 2, and 4 supernatants were harvested and the concentrations of interferon-y (A), GM-CSF (B), TNF-a (C), and interleukin-4 (D) were determined by ELISA. Abbreviations GM-CSF, granulocyte monocyte colony stimulating factor TNF-a, tumor necrosis factor-a. Source From Ref. 6.

Fig. 11.2. Domain structure of cytokine receptors. Schematic representation of the domain structure of selected cytokine receptors. WS motif conserved WSXWS sequence (W tryptophan S serine X non-conserved amino add) IL interleukin EpoR receptor for erythropoietin GHR growth hormone receptor LIF-R leukemia inhibitory factor receptor G-CSFR granulocyte colony stimulating factor receptor IFNR interferon receptor TNFR tumor necrosis factor receptor NGFR nerve growth factor receptor Fas, CD40 transmembrane receptors of lymphocytes.

Broudy VC, Kaushansky K, Segal GM, Harlan JM, Adamson JW. Tumor necrosis factor type alpha stimulates human endothelial cells to produce granulocyte/macrophage colony-stimulating factor. Proceedings of the National Academy of Sciences of the United States of America 1986, 83, 7467-7471. 

M19. Muller, C. A., Uhl, W., Printzen, G., Gloor, B., Bischofberger, H., Tcholakov, O., and Biichler, M. W., Role of procalcitonin and granulocyte colony stimulating factor in the early prediction of infected necrosis in severe acute pancreatitis. Gut 46,233—238 (2000). 

Several cytokine genes have been found to reduce tumors by stimulating localized inflammatory and/or immune responses. These include interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-7, IL-12, interferon gamma (IFN-y), tumor necrosis factor-a (TNF-a), and granulocyte-macrophage colony-stimulating factor (GM-CSF). 

Combined therapy with clozapine and fluvoxamine (n = 11) and clozapine monotherapy (n = 12) have been monitored before and during the first 6 weeks of medication (39). The co-administration of fluvoxamine attenuated and delayed the clozapine-induced increase in plasma concentrations of tumor necrosis factor-alpha, enhanced and accelerated the clozapine-induced increase in leptin plasma concentrations without a significant effect on clozapine-induced weight gain, and reduced granulocyte counts. 

After binding and phagocytosis, alveolar macrophages and monocytes release pro-inflammatory cytokines, e.g. lL-1, interferon-y and tumor necrosis factor-a (fig. 1). These cytokines activate resident cells (epithelial cells, fibroblasts) to produce chemokines such as lL-8, granulocyte-monocyte-colony-stimulating factor, RANTES (regulated on activation normal T cell expressed and secreted) that will result in a second wave of cell recruitment (mononuclear and polymorphonuclear cells). 

MIC caused dose-dependent necrosis of brain cells and muscle cells (Anderson et al, 1988) of rats in culture these findings could explain neuromuscular complaints in Bhopal victims. Exposure of mice to 1-3 ppm MIC was found to inhibit erythroid precursors, pluripotent stem cells and granulocyte-macrophage progenitor recovery from this inhibitory effect was found within 3 weeks after 1 ppm but not after 3 ppm (Hong et al, 1987). At higher concentrations of 6-15 ppm, MIC inhibited cell cycling in bone marrow, alveolar cells, and T lymphocytes (Conner et al., 1987 Shelby et al, 1987) similar data were reported by others (Tice et al, 1987 Mason et al, 1987). MIC can inhibit bone marrow cell proliferation in mice (Meshram and Rao, 1988). MIC can cause necrosis in whole-brain cell cultures (Anderson et al, 1990) and inhibit differentiation in muscle cell cultures (Anderson et al, 1988). 

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