Adhesion

Figure 5: Schematic representation of the molecular mechanism of leucocyte adherence in post capillary venules. a) shows the rolling leucocyte with expression of P-Selectin on the endothelium which interacts with sialyated Lewis. b) shows induced expression of E- Selectin by endotoxin, IL-1$\beta$ and TNF$\alpha$. In c) the leucocyte has grabbed tightly onto the endothelium When E-Selectin on the endothelium is bound to L-Selectin on the leucocytes there is increased affinity of the leucotye for ICAM-1 and like molecules presumabley due to the induction of the expression of $\beta_2$ intigrins on the leucocyte.

During inflammation leucocytes undergo various morphological changes associated with adherence, firstly they adopt a more spherical shape, then they roll, then they become stationary and flatten. During this process the membrane takes on a ruffelled appearance and there is a change in membrane receptors.

Binding of E-selectin with L-selectin results in very slow rolling and the onset of adherence. Tight adherence of leucocytes is thought to occur only after rolling. Following the interaction of E and L selectin, interaction of $\beta_2$ integrins (LFA-1, Mac-1) on leucocytes with ICAM-1 on the endothelium and the $\beta_1$ integrin (VLA-4) with VCAM-1 on the endothelium are thought to result in adherence of leucocytes onto the endothelium. It has been noted that binding of E to L selectin results in increased binding of $\beta_2$ integrins to ICAM-1.