ABSTRACT
Adhesion molecules are expressed and shed from endothelial cells, platelets neutrophils and monocytes. It is not clear what the major source of circulating adhesion molecules is and, when the plasma level is increased, whether this is due to increased cellular expression or to increased shedding from cell surfaces. Although plasma-soluble E-selectin is 50% higher in obese women than in lean women, baseline gene expression for E-selectin and vascular cell adhesion molecule 1 (VCAM-1) and intracellular adhesion molecule 1 (ICAM-1) in fat is lower than in lean women and actually increases with weight loss induced by a very low calorie diet (VLCD) (Bosanská et al. 2008). However, overexpression of pro-infl ammatory factors is seen in subcutaneous adipose tissue of obese subjects in cells of the monocyte/macrophage lineage and weight loss with VLCD lowered pro-infl ammatory factors and increased anti-infl ammatory factors (Viguerie et al. 2005). ICAM-1 is certainly expressed on endothelial cells in culture (Dustin 1986) and can be observed on the surface of atherosclerotic plaques (De Graba 1997). Cellular adhesion molecules (CAMs) can be induced by the transcription factor NF kappa beta. Th e production and release of CAMs from endothelial cells has been found to be inducible by interleukin-1, tumour necrosis factor alpha (Cartwright et al. 1995), angiotensin II (Pastore et al. 1999) and non-oxidized low density lipoprotein (Maeno et al. 2000). Leeuwenberg et al. (1992) found that sICAM1 and sE-selectin correlated with surface expression on cultured endothelial cells, as did Noutsias et al. (2003) in dilated cardiomyopathy. Th is suggests that there is no specifi c control mechanism for shedding but there is evidence in neutrophils of control of the process of shedding. In neutrophils p38 activation (via FMLP, LPS and hypertonicity) and protein kinase C (PKC) activation lead to shedding of L-selectin through a protease or sheddase. One example of this is the ADAM family of proteases (A Disintegrin and Metalloprotease) (Edwards et al. 2008). Th e archetypal ADAM is ADAM17. Th is protease shed the TNF-alpha precursor from the surface to produce the active cytokine and is also referred to as TNF-alpha converting enzyme (TACE) (Bell et al. 2007). While a number of ADAMs have been identifi ed in mammalian tissues, this was the fi rst to have a known function. TACE is also involved in VCAM-1 shedding (plus 20 other proteins) (Garton et al. 2003). In systemic infl ammatory conditions, for example, juvenile rheumatoid arthritis and sepsis particularly with organ failure (Whalen et al. 2000), CAMs are elevated but it is not clear whether the source is white cells or the endothelium. It would appear that platelets are the major source of circulating P-selectin in healthy individuals. Endothelial cell activation from sepsis (as assessed by increased levels of circulating E-selectin and ED1-fi bronectin) is associated with an increased sPselectin concentration per platelet (Fijnheer et al. 1997).
