Myeloid cells

A particularly active area of research concerns the elucidation of the mechanisms of refractoriness or resistance to anti-VEGF therapy. Tumor cell-intrinsic or treatment-induced expression of angiogenic factors may be implicated Very recent studies have provided evidence that, at least is some murine models, refractor-inessm to anti-VEGF therapy is related to the ability of the tumor to recruit CDllb+Grl+ myeloid cells, which promote angiogenesis [5]. It remains to be established whether these findings also apply to human tumors. 

Shojaei F, Wu X, Malik AK et al (2007) Tumor refrectoriness to anti-VEGF treatment is mediated by CDllb+ Grl+ myeloid cells. Nat Biotechnol 8 911-920... 

Included among other differentiating cell lines which have been established in culture, is the human promyelocytic cell line HL-60, which differentiates into more mature myeloid cells upon treatment with retinoic acid and prostaglandin E] (PGEi). Friend erythroleukemia cells differentiate into hemoglobin-producing cells when treated with either dimethyl sulfoxide, or hexamethylene bis-acetamide. 

Lactoferrin j Iron-binding protein May inhibit growth of certain bacteria by binding iron and may be involved in regulation of proliferation of myeloid cells... 

Hematopoiesis is defined as the development and maturation of blood cells and their precursors. In utero, hematopoiesis may occur in the liver, spleen, and bone marrow. However, after birth, it occurs exclusively in the bone marrow. All blood cells are generated from a common hematopoietic precursor, or stem cell. These stem cells are self-renewing and pluripotent and thus are able to commit to any one of the different lines of maturation that give rise to platelet-producing megakaryocytes, lymphoid, erythroid, and myeloid cells. The myeloid cell line produces monocytes, basophils, neutrophils, and eosinophils, whereas the lymphoid stem cell differentiates to form circulating B and T lymphocytes. In contrast to the ordered development of normal cells, the development of leukemia seems to represent an arrest in differentiation at an early phase in the continuum of stem cell to mature cell.1... 

Ruiz DA, Luttun A, Carmeliet P. An SDF-1 trap for myeloid cells stimulates angiogenesis. Cell 2006 124 18-21. 

Nyame, A.K., Pilcher, J.B., Tsang, V.C.W. and Cummings, R.D. (1996) Schistosoma mansoni infection in humans and primates induces cytolytic antibodies to surface Le(x) determinants on myeloid cells. ExperimentalParasitology82,191-200. 

Consistent with their role as immune receptors, each human TLR is expressed by at least one subset of myeloid cells (MCs) or lymphocytes [7,8]. TLRs are also present on stromal elements like endothelium particularly after local inflammatory stimulus [9-11]. These distribution patterns can determine the physiological consequences of stimulation or antagonism, and affect the balance of toxicity versus therapeutic effect. Another consideration for medicinal chemistry is subcellular localization of TLRs. While most are expressed on the cell surface, some (TLRs 3,7,8, and 9) can localize to endosomes where they survey ingested material for ligands, so drug access to this compartment can be crucial when targeting these TLRs [12]. 

Leukotriene B4 has been implicated in inflammatory processes and chemo-taxis. The G-protein-coupled receptor in human myeloid cells was postulated to possess two distinct binding sites. Photoaffinity studies using unmodified tritiated LTB4 as photoreactive species labeled two different proteins in the presence (53 kDa) and in the absence of a non-cleavable GTP analogue (56 kDa). This means that stabilization of the G-protein in the GTP-bound state resulted in an interconversion of the first high affinity binding site to an alternative low-affinity binding site [99]. 

Flow cytometry is now commonly used in immunotoxicity studies to assess changes in relative frequency and number of lymphoid and myeloid cells in the spleen, lymph nodes, bone marrow and/or peripheral blood of rodents, and in the peripheral blood of humans. A list of selected cell surface markers useful in immunotoxicity studies is shown in Table 7.3. Notably, the majority of available reagents are specific for murine antigens with human reagent availability a close second. Reagents for rat, primate, and... 

While changes in cell phenotypes have proved useful in some settings to characterize the immunotoxicity of xenobiotics,1 phenotypic analysis alone is often not a sensitive indicator of low dose immunotoxicity for many agents that alter immune function. Xenobiotics that exert selective toxicity on lymphoid and myeloid cells may be discovered through immunophenotypic analysis. However, most agents produce immunotoxicity at doses much lower than those required to produce cytotoxicity or interfere with primary lymphoid organ differentiation. Some of the most potent immunosuppressive chemicals that have been tested, such as cyclosporine A, do not alter immunophenotype at doses that are immunosuppressive. On the other hand, when phenotyping is linked to assessment of functional parameters of the cells, immunotoxic effects are more likely to be identified. 

There are literally hundreds of markers that are currently available for the mouse and human than can be used to characterize lymphoid and myeloid cells and subsets in primary and secondary lymphoid organs. Many of the markers expressed in mammals are highly conserved across species and have been designated as genetic clusters of differentiation (CD). CDs can be identified with fluorescently labeled monoclonal antibodies. As presented previously, when combined with other fluorescent probes, important information on intracellular biochemistry and cell function can be obtained. Many of the biochemical markers used by immunotoxicologists are common to other... 

M. A. S., Mertlesmann, R., Welte, K. (1986). Recombinant human granulocyte colony-stimulating factor Effects on normal and leukaemic myeloid cells. Science 232,61-5. 

Valore, E. V., Ganz, T. (1992). Posttranslational processing of defensins in immature human myeloid cells. Blood 79,1538-44. 

Cassatella, M. A., Hartman, L., Perussia, B., Trinchieri, G. (1989). Tumor necrosis factor and immune interferon synergistically induce cytochrome b.245 heavy-chain gene expression and nicotinamide-adenine dinucleotide phosphate hydrogenase oxidase in human leukemic myeloid cells. J. Clin. Invest. 83,1570-9. 

Perussia, B., Dayton, E. T., Lazarus, R., Fanning, V., Trinchieri, G. (1983). Immune interferon induces the receptor for monomeric IgGl on human monocytic and myeloid cells. J. Exp. Med. 158,1092-113. 

Leucocyte All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. 

Boidier, C., and Laurent, G., 1996, Daunombicin-induced intemucleosomal DNA fragmentation in acute myeloid cell lines. Leukemia 10 417-425. 

Anti-CD30 (Ki- ) (49) and Anti-CD15 (Leu-Ml) (50) both react with Reed-Stemberg cells of Hodgkin s Disease. Leu-Ml also reacts with myeloid cells and is a very specific, though not very sensitive, marker for adenocarcinomas. 

II.lt Treml2 +24 kb F 17C 0 Triggering receptor expressed on myeloid cells like 2, signalling 2... 

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