Endothelial cells, sensitivity

The ETa receptor activates G proteins of the Gq/n and G12/i3 family. The ETB receptor stimulates G proteins of the G and Gq/11 family. In endothelial cells, activation of the ETB receptor stimulates the release of NO and prostacyclin (PGI2) via pertussis toxin-sensitive G proteins. In smooth muscle cells, the activation of ETA receptors leads to an increase of intracellular calcium via pertussis toxin-insensitive G proteins of the Gq/11 family and to an activation of Rho proteins most likely via G proteins of the Gi2/i3 family. Increase of intracellular calcium results in a calmodulin-dependent activation of the myosin light chain kinase (MLCK, Fig. 2). MLCK phosphorylates the 20 kDa myosin light chain (MLC-20), which then stimulates actin-myosin interaction of vascular smooth muscle cells resulting in vasoconstriction. Since activated Rho... 

Ramegowda B, Samuel JE, Tesh VL Interaction of Shiga toxins with human brain micro-vascular endothelial cells Cytokines as sensitizing agents. J Infect Dis 1999 180 1205— 1213. 

The IL-ls induce their characteristic biological activities by binding to specific cell surface receptors present on sensitive cells. Two distinct receptors, type I and II, have been identified. Both IL-la and IL-ip can bind both receptors. The type I receptor is an 80 kDa transmembrane glycoprotein. It is a member of the IgG superfamily. This receptor is expressed predominantly on fibroblasts, keratinocytes, hepatocytes and endothelial cells. The type II receptor is a 60 kDa transmembrane glycoprotein, expressed mainly on B-lymphocytes, bone marrow cells and polymorphonuclear leukocytes. It displays a very short (29 amino acid) intracellular domain,... 

TNF fails to induce death of all tumour cell types. Although many transformed cells are TNF sensitive, the cytokine exerts, at best, a cytostatic effect on others and has no effect on yet others. The cytotoxic activity is invariably enhanced by the presence of IFN-y. The concurrent presence of this interferon increases the range of transformed cell types sensitive to TNF-a, and can upgrade its cytostatic effects to cytotoxic effects. It can also render many untransformed cells, in particular epithelial and endothelial cells, susceptible to the cytotoxic effects of TNF-a. 

P2Y receptors that are found on endothelial cells elicit a Ca2+-dependent release of endothelium-dependent relaxing factor (EDRF) and vasodilation. A secondary activation of a Ca2+-sensitive phospholipase A2 increases the synthesis of endothelial prostacyclin, which limits the extent of intravascular platelet aggregation following vascular damage and platelet stimulation. The P2Y-mediated vasodilation opposes a vasoconstriction evoked by P2X receptors located on vascular smooth muscle cells. The latter elicit an endothelial-independent excitation (i.e. constriction). P2Y receptors are also found on adrenal chromaffin cells and platelets, where they modulate catecholamine release and aggregation respectively. 

Thiols, protein or small molecular weight, can be S-nitrosated either by reaction with N O-oxidation products (Scheme 4.1) in hydrophobic domains of plasma proteins or transnitrosated at the cell-plasma interface of NO-producing cells (endothelial cells) or NO-storing cells (RBCs). Efforts to determine the true levels in plasma and in the various cellular compartments are complicated owing to thermal sensitivity and photosensitivity (Sexton et al., 1994 Alpert et al., 1997 Mutus et al., 1999) of the RS-NO bond. Techniques currently employed for the detection and quantification of RSNOs have been summarized in recent reviews (Martinez Riuz and Lamas, 2004 Rasaf et al., 2004). 

The apoptotic effect of 4-HNE and related aldehydes occitts at concentrations over 10 to 20 pM and depends on the ceU type, endothelial cells and fibroblasts being very sensitive to low 4-HNE concentrations (Esterbauer et al, 1991). Oxidized LDL exhibit certain amoimts of 4-HNE (range between 10 to 50 pM depending on the oxidation stage) which are compatible with an involvement of this aldehyde in the cytotoxicity (Jurgens et al, 1987). Moreover, local tissue concentrations of 4-HNE may reach concentrations higher than 100 pM, in particular in membranes because of its high hydrophobicity (Benedetti et al, 1986). 

CD31 (54), Factor Vlll-related antigen (55), and CD34 (56) cannot often be demonstrated in poorly differentiated vascular tumors. The use of the lectin Ulex europaeus agglutinin 1 (UEA-1) (57) is a more sensitive method to detect endothelial cells. Like other lectins, however, UFA-1 reacts with many other cell types. 

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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