Inflammation cells involved

In the vasculature, ANG H not only increases contraction of smooth muscle cells, but is also able to induce vascular injury. This can be prevented by blocking NFkB activation [3] suggesting a link between ANG II and inflammation processes involved in the pathogenesis of arteriosclerosis (see below). Thus, ACE inhibitors not only decrease vascular tone but probably also exert vasoprotective effects. 

The P2X7 receptor is a ligand-gated ion channel present in cells involved with inflammation. The receptor is activated by extracellular ATP, which leads to the processing and release of IL-1 (5. Baxter et al. [63] report on the parallel optimization of binding affinity, efficacy, physicochemical properties, ADME properties, and PK (Scheme 18). 

Similar to drug targeting strategies aimed at multiple target epitopes, a drug that intervenes at various stages of cell activation may be exploited for effective blockade of endothelial cell involvement in chronic inflammation. 

Basophil—Type of white blood cell involved in the defense at a site of injury plays a role in inflammation. 

Aspirin has been used to treat arthritis for approximately 100 years, but its mechanism of action—inhibition of COX activity—was not discovered until 1971. COX-2 appears to be the form of the enzyme most associated with cells involved in the inflammatory process although, as outlined above, COX-1 also contributes significantly to prostaglandin biosynthesis during inflammation. 

The cell damage associated with inflammation acts on cell membranes to cause leukocytes to release lysosomal enzymes arachidonic acid is then liberated from precursor compounds, and various eicosanoids are synthesized. As discussed in Chapter 18, the cyclooxygenase (COX) pathway of arachidonate metabolism produces prostaglandins, which have a variety of effects on blood vessels, on nerve endings, and on cells involved in inflammation. The lipoxygenase pathway of arachidonate metabolism yields leukotrienes, which have a powerful chemotactic effect on eosinophils, neutrophils, and macrophages and promote bronchoconstriction and alterations in vascular permeability. 

In addition to direct effects on genes regulating inflammation, glucocorticoids also inhibit the transcription factors that initiate synthesis of pro-inflammatory cytokines (e.g., interleukin-1, tumor necrosis factor), enzymes (e.g., COX-2, nitric oxide synthase), and receptor proteins (e.g., natural killer receptors).17,87,89 Glucocorticoids may also exert some of their effects via a membrane-bound receptor that regulates activity of macrophages, eosinophils, T lymphocytes, and several other types of cells involved in the inflammatory response.89 Consequently, glucocorticoids affect many aspects of inflammation, and their powerful anti-inflammatory effects in rheumatoid arthritis result from their ability to blunt various cellular and chemical components of the inflammatory response. 

Several agents are now available that inhibit the action of tumor necrosis factor-alpha (TNF-a). TNF-a is a small protein (cytokine) that is released from cells involved in the inflammatory response. TNF-a seems to be a key chemical mediator that promotes inflammation and joint erosion in rheumatoid arthritis.83 Drugs that inhibit this chemical will therefore help delay the progression of this disease by decreasing TNF-a s destructive effects.70... 

Plaque ruptures in the ACS setting are often involved with a diffuse process, Inflammation is involved in plaque growth and development in addition to complications of plaque rupture. These could be considered the result of injury, Well-known coronary risk factors can provide the impetus for plaque development. Cigarette smoking, hypertension, hyperlipidemia, hyperglycemia, or insulin resistance are noxious stimuli. The stimuli can facilitate monocyte attachment to endothelial cells. Eventually monocytes migrate to the subintimal space and become foam cells to initiate plaque development. 

Under physiological conditions there is a small resident population of macrophages— microglia and perivascular macrophages—along with some roaming T cell lymphocytes in the central nervous system. However, most of the immune cells involved in inflammation after stroke are in fact derived from the systemic circulation. 

Immune cells involved in stroke-related inflammation stroke are predominantly derived from the circulating blood. 

In order to develop meaningful assay systems to study mechanisms involved in chronic inflammation, cells from cartilage, bone, normal synovium, and from organized inflammatory lesions as well as leukocytes from spleen, thymus, and macrophages from serous cavities of laboratory animals maintained as stable populations in cell or organ culture have been utilized. 

Cytokines are chemicals released by damaged cells and cells involved in inflammation and repair. Drugs have been developed against two of them, tumour necrosis factor a (TNF-a) and interleukin 1 (IL-1). These two cytokines are released from macrophages and together they are key players in the inflammatory response. Levels of both are raised in rheumatoid arthritis and other autoimmune diseases. 

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