Leucocyte rolling

After infection and immune cell activation, endothelial cells are variously activated to bind peripheral blood leucocytes. Bacterial toxins such as lipopolysaccharide (LPS), inflammatory cytokines such as tumour necrosis factors a and (5 (TNFa and TNFP) and interleukin-1 (5 (IL-ip) increase the synthesis of cell surface E- and P-selectins in endothelial cells. Histamine and thrombin increase PM P-selectins in endothelial cells and platelets. L-selectins are constitutively expressed in monocytes and lymphocytes. The selectins are involved in the initial adhesion of leucocytes with endothelial cells via selectin-selectin receptor interactions, for example, monocyte L-selectin-endothelial L-selectin ligand binding and T-lymphocyte-endothelial selectin-integrin interactions. This initial phase of leucocyte-endothelial adhesion enables an early stage of leucocyte rolling through successive formation and breakage of adhesive interactions. 

The recruitment and migration of leucocytes into inflamed tissues is a carefully orchestrated process (Figure 7.1). It consists of sequential steps mediated by different families of adhesion molecules expressed by both the leucocytes and the endothelial cells at the site of inflammation [4]. Of these adhesion molecules, the selectin family mediates the initial contact and subsequent rolling of the leucocyte on the endothelium. It consists of three members, i.e. E- (endothelial), P- (platelet) and L- (leucocyte) selectin. Activated endothelial cells express E- and P-selectin. P-selectm is also expressed on platelets, whereas L-selectin is only expressed on subsets of leucocytes [5]. 

The majority of more recent structures relate to the sialyl Lewis X blood group carbohydrate receptor function for the selectin family of eukaryote lectins that mediate leucocyte-endothelial cell interaction during the initial stages of extravasation ( neutrophil rolling ) (20). These structures are the sialyl Le , Le, and Le sequences and several 6 sulfo GlcNAc and 3 sulfo Gal derivatives found in both protein and sphingolipid glycoconjugates (21-24). 

An in vitro study of the effect of ABC/3TC and TDF/FTC on leucocyte recruitment found that ABC /3TC and ABC alone had significant effects on rolling and adhesion of leucocytes (TDF/FTC did not) and enhanced expression of CDllb/CD18 in neutrophils and monocytes. The authors suggest that this gives evidence of a worse vascular profile for ABC/3TC than for the other drug combinations tested [145 ]. 

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