Endothelial Cell Sources

Endothelial cells in culture need a constant supply of growth factors such as FGFs and VEGF in order to continue cell cycling. In most cultures the addition of serum to the culture medium is sufficient to maintain a low level of endothelial cell proliferation. Cells cultured this way can be subcultured at a split ratio of 1 3 for four to five passages without significant 

Endothelial cells can also be prepared from tissue from other species. Capillary endothelial cells of bovine origin are used quite frequently, because these cells are rather sensitive to treatment with angiogenesis inhibitors such as angiostatin and endostatin (Griffioen et al., unpublished results). It should be noted however, that species-dependent responses to drugs can occur. 

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Endothelial cells are the major source of ET-1-synthesis. ET-1 is also produced by astrocytes, neurons, hepatocytes, bronchial epithelial cells, renal epithelial and mesangial cells. Physiological stimuli of ET-1-synthesis in endothelial cells are angiotensin II, catecholamines, thrombin, growth factors, insulin, hypoxia and shear stress. Inhibitors of ET-1 synthesis are atrial natriuretic peptide, prostaglandin E2 and prostacyclin. ET-2 is mainly synthesized in kidney, intestine, myocardium and placenta and ET-3 is predominantely produced by neurons, astrocytes and renal epithelial cells. 

In the very early phases of the acute inflammatory response most of the cells invading the damaged area are polymorphonuclear neutrophils, also denoted as PMNs, which serve as initial line of defense and source of proinflammatory cytokines. These cells, which usually live for 4-5 days, circulate in the blood until they are attracted by chemokines into injured tissues. Whereas physical injury does not recruit many neutrophils, infections with bacteria or fungi elicit a striking neutrophil response. The characteristic pus of a bacterial abscess is composed mainly of apoptotic (apoptosis) and necrotic PMNs. Emigration of neutrophils from the blood starts with a process denoted as margination where neutrophils come to lie at the periphery of flowing blood cells and adhere to endothelial cells (Fig. 1). L-Selectin is expressed... 

It has been proposed that NO mediates the myocardial depression associated with sepsis (F6, L14). NO synthesis induced by endotoxin blunts beta-adrenergic responsiveness (B2). In vivo, the use of NO synthase inhibitors led to conflicting results (M26), with a general decreased cardiac output and oxygen delivery being observed. NO synthase inhibition improved left ventricular contractility in endo-toxemic pigs but also increased ventricular afterloads, which ultimately is detrimental to cardiac function (H20). Possible sources of NO in the heart may be the vascular cells, the endothelial cells, and the cardiac myocytes (P6). 

Another prominent site of deposition of (5-amyloid fibrils with age and in AD is within the cerebrovasculature in areas of the brain prone to parenchymal amyloid deposition [137-139]. The peptide deposits along the surfaces of the smooth muscle cells of the vascular wall, resulting in the death of those cells and their replacement by amyloid fibrils, weakening the vascular wall. Endothelial cells are also affected [140]. The Dutch mutation in the APP precursor protein Q22E, within the (5-peptide sequence, produces a particularly fibrillogenic and toxic (to smooth muscle cells) peptide associated with primarily vascular deposition of mutant peptide and hemorrhagic vessel disease [137]. Thus, in addition to neuronal cells, the brain vascular smooth muscle cells are a pathologically relevant cell type. While the source of... 

Another metabolite of arachidonic acid is prostacyclin (PGI2). As with TxA2, PGI2 is produced continuously. Synthesized by vascular smooth muscle and endothelial cells, with the endothelium as the predominant source, PGI2 mediates effects that are opposite to those of TxA2. Prostacyclin causes vasodilation and inhibits platelet aggregation and, as a result, makes an important contribution to the antithrombogenic nature of the vascular wall. 

A wide range of cells are capable of producing IL-l (Table 9.4). Different cell types produce the different IL-ls in varying ratios. In fibroblasts and endothelial cells, both are produced in roughly similar ratios, whereas IL-ip is produced in larger quantities than IL-la in monocytes. Activated macrophages appear to represent the major cellular source for IL-1. 

It is now recognised that the function of the immune system is carefully regulated by cytokines, small (8.5-40 kDa) proteins secreted by immune cells and by tissue cells such as endothelial cells and fibroblasts. T helper cells and macrophages are major sources of cytokines during inflammatory... 

GM-CSF is undetectable in the serum of normal humans, and no normal cells have been shown to express this protein constitutively. Some transformed cells may constitutively express GM-CSF, and it is actively synthesised and secreted by antigen- and lectin-stimulated T cells and by endothelial cells and fibroblasts exposed to TNF, IL-1 or endotoxin. Other sources of GM-CSF include stimulated B lymphocytes, macrophages, mast cells and osteoblasts, whilst TNF and IL-1 can stimulate its production by acute myeloid leukaemia cells. Some solid tumours and synovial cells from rheumatoid joints may also express GM-CSF and this may be important in disease pathology. 

Tumour necrosis factor (TNF) was originally described as a factor produced following exposure of Bacille-Calmette-Guerin-treated animals to bacterial endotoxin. It was so named because it possessed the ability to necrotise tumours. This factor is now named TNF-a to distinguish it from another, related cytokine lymphotoxin, which is sometimes referred to as TNF-/J Alternative names for TNF-a include cachectin and cytotoxin. Its primary cellular source in the body is the activated macrophage, but some other cell types (e.g. NK cells, astrocytes, some lymphocytes, fibroblasts, many tumour cells, endothelial cells and neutrophils) have also been shown to synthesise this cytokine. 

M. P. Lisanti, P. E. Scherer, J. Vidugiriene, Z. tang, A. Hermanoski-Vosatka, Y.-H. Tu, R. F. Cook, and M. Sargiacomo. Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source implications for human disease. J. Cell Biol. 126 111-126(1994). 

Production of blood cells in bone marrow of the central axial skeleton is referred to as medullary hematopoiesis. Hematopoietic tissue in adult bone marrow is well perfused and contains fat cells (adipocytes), and various types of blood and blood precursor cells encased within a protein matrix. Fibroblast, stromal and endothelial cells within bone marrow, serve as sources of matrix proteins as well as a factory for growth factors and chemokines that regulate blood cell production and release matured cells into the circulation [2,3]. Chemokines act as signal lamps for trafficking of lymphocytes in and out of lymphoid tissues. Erythroblasts, neutrophils, lymphoblasts, macrophages, megakaryocytes, and pluripotent stem cells are also found within the calcihed lattice crisscrossing the marrow space. 

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