Rolling

The first step in the movement of the leucocyte to the injured tissue involves the rolling process. In this the leucocyte is seen to roll along the epithelium, this behavior is not seen in healthy tissues.

Rolling may be identified on intra-vital microscopy by looking at the leucocyte velocity. In a 30 $\mu$ post capillary venule, red blood corpuscules travel at about 1-3 mm s^-1. Leucocytes roll at velocities between 5-300 mm s^-1 with the most common velocity range of 20-60 mm s^-1.

The rolling process is believed to be due to the interaction between molecules expressed on leucocytes and the endothelium. E and P selectins are expressed on the endothelium. These interact with L-selectin and the carbohydrate derivative sialyated Lewis on the leucocyte. Both sialyated Lewis and L-selectin are constitutively expressed. It is believed that L-selectin interacts with E and P selectin via sialyated carbohydrate moieties on these molecules.

P selectin is released from the Weibel-Palade body in the endothelial cell on stimulation by hypoxia, free radicals, peroxides, histamine and thrombin. Endotoxin, IL-1$\beta$ and TNF-$\alpha$ induce the expression of E-selectin on the endothelium. P-selectin interacts with sialyated Lewis and E-selectin interacts with L-selectin. The interaction is visible as rolling, see figure 7. It is felt that interaction with E-selectin plays a part in adherence as well as rolling.

L-selectin acts as a ligand for both E and P-selectins. Following capture of the leucocyte on the endothelium L-selectin is rapidly shed from the leucocyte on stimulation by LTB4, C5a, TNF-$\alpha$, IL-1 and PAF.

Figure 8: 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.