Adhesion and movement of inflammatory leucocytes

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. 

Integrins are heterodimeric (aP) complexes expressed on leucocytes. Monocytes and lymphocytes express pi integrins and all leucocytes express integrins having a common P2 chain but different a chains. Integrins are involved in cell-matrix as well as cell-cell interactions. The synthesis of P1 and P2 integrins is stimulated by endothelium-derived leucocyte chemoattractants such as monocyte chemoattractant protein-1 (MCP-1). The endothelium ICAM-1 is subject to upregulation by leucocyte-derived cytokines. 

The interaction of the various aP integrin complexes with ICAMs results in firm attachment and spreading. Subsequent VCAM-1-integrin and PECAM-1-integrin interactions are involved in leucocyte transmigration through endothelial cell junctions into the extravascular space. Leucocytes can thence proceed to interact with target cells and initiate inflammatory processes. 

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