Monocytes, adherent

The cytokines TNF-a and TNF- 3 are inflammatory mediators produced by macrophages and other cells in response to invasive stimuli such as bacterial LPS and endotoxins, antigen-antibody complexes, products of complement activation and cytokines. TNF activates leucocytes, increases neutrophil and monocyte adherence and migration and stimulates the synthesis of other pro-inflammatory cytokines. TNF-a is membrane-located and interacts with a PM-located receptor (GDI 20) leading to activation of caspases (cysteine proteases critically involved in cell death) and activation of PLA2. 

G3. Gamble, J. R., Elliott, M. J., Jaipargas, E., Lopez, A. F., and Vadas, M. A. Regulation of human monocyte adherence by granulocyte-macrophage colony-stimulating factor. Proc. Natl. Acad. Sci. U.SA. 86, 7169-7173 (1989). 

The amount of ATP release from human platelets on SPEAs (an indication of hemocompatibility) was 2-fold lower than on the above nondegradable polymers. In addition, monocytes adherent onto saturated PEA induced far less secretion of proinflammatory cytokines such as interleukin (IL)-6 and IL-1 when compared with the tissue culture-treated polystyrene control. Therefore, saturated PEAs appear to support a more natural wound healing process by promoting reendothelialization and lowering inflammatory response. 

What causes damage to endothelial cells, how do platelets and monocytes adhere to arterial wall, how is cell damage repaired What causes medial myocy-tic migration into the intima, how and why does cholesterol enter some cells and not others, how does endothelium rupture, why and how does clot accrete and dissolve What is the time course of myocardial cell anoxia, destruction and recovery and how does this affect myocardial infarction. 

ICAM-1 and lymphocyte function-associated protein (LFA)-l pathway are involved in monocyte-endothelium interaction during a cholesterol-rich diet. In rats on high-cholesterol diet, ICAM-1 expression was increased on aortic EC, which was associated with increased monocyte adherence (more than 85% of adherent macrophages exhibited LFA-1 antigen and injecting the animals with ICAM-1 monoclonal antibody and LFA-1 monoclonal antibody reduced mostly LFA-1 positive macrophages) (167). In clinically healthy middle-aged men, levels of soluble ICAM-1 (sICAM-1), but not sVCAM-1 or E-selectin, were associated with subclinical atherosclerosis and inflammatory variables (168). 

Elevated ET-1 in SCA patients, even in the steady state, may play an important role in the dehydration of sickle erythrocytes and the resulting enhanced intra-erythrocytic HbS polymerization. Indeed, it has been shown that ET-1 activates Ca2+- gated K+ channels in mouse erythrocytes [34]. ET-1, as a pro-inflammatory agonist, has been shown to induce the production of inflammatory cytokines by monocytes. One of the cytokines, namely TNFa enhances the adherence of sickle erythrocytes to vascular endothelium [35]. In addition, endothehns upregulate the expression of endothelial adhesion molecules such as ICAM-l, VCAM-1 and E-se-lectin, which participate in the recruitment of white cells to the site of inflammation. The overall conclusions that can be drawn from these data is that ET-1 plays a critical role in the vasospasm and inflammation that result in VOC. The major effect of HU in ameliorating the clinical symptoms of SCA likely results from its ability to inhibit the chronically activated ET-1 expression in SCA patients. 

Lee, K.-D., Nir, S. and Papahadjopoulos, D. (1993). Quantitative analysis of liposome-cell interactions in vitro rate constants of binding and endocytosis with suspension and adherent J774 cells and human monocytes, Biochemistry, 32, 889-899. 

TNF-a is chemotactic for monocytes and neutrophils. Its effects on neutrophils are numerous for example, it can prime degranulation and reactive oxidant production, enhance phagocytosis and ADCC and up-regulate the expression of some surface receptors, such as CR3. Whilst low concentrations of TNF-a are required to prime the cells subsequent to stimulation by other agonists, such as fMet-Leu-Phe, higher concentrations of TNF-a alone can activate low levels of oxidant production. This activity is even more pronounced if the neutrophils are adhered to surfaces. 

Lp(a) can also influence the adherence of monocytes to endothelial cells in vitro (K7). 

As described above, halichlorine was shown to inhibit LPS-induced events in BAECs, including adhesion-molecule expression, adherence of monocytes, and NF- activation. Thus, halichlorine is thought to be an attractive candidate for the adjunctive therapy of diseases such as atherosclerosis. 

Deplete the cell suspension of monocytes and macrophages by incubation in 150-cm2 tissue culture flask for 2 h at 37°C (monocytes and macrophages will adhere to the surface of the flask). Wash off the nonadherent cells with PBS buffer and collect. 

Phorbol esters are tumor promoters capable of binding to and activating protein kinase C (PKC), one critical component in T cell activation.55,56 PMA is a structural analogue of diacylglycerol (DAG), an allosteric activator of PKC. PKC activation via phosphorylation leads to calcium release, resulting in a cascade of cellular responses including rapid proliferation.56 Experimentally, phorbol esters have been used as chemoattractants and to differentiate nonadherent monocytes to adherent macrophage cultures.55,57-60... 

Brodbeck WG, Nakayama Y, Matsuda T, Colton E, Ziats NP, Anderson JM. Biomaterial surface chemistry dictates adherent monocyte/macrophage cytokine expression in vitro. Cytokine 2002, 18, 311-319. 

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