Weight Loss and Adhesion Molecules - Adhesion Molecules - page 218

INTRODUCTION
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-inl 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-inl ammatory factors and increased anti-inl 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. h 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. h is suggests that there is
no specii 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). h e
archetypal ADAM is ADAM17. h 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 identii ed in mammalian tissues, this was the i rst to have a known function.
TACE is also involved in VCAM-1 shedding (plus 20 other proteins) (Garton et al.
2003). In systemic inl 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-i bronectin) is associated with an increased sP-
selectin concentration per platelet (Fijnheer et al. 1997).