Rolling

Figure 4: Schematic representation of the molecular mechanism of rolling in leucocytes in post capillary venules. a) shows the unactivated state with no expression of selectins on the leucocyte of the endothelium. b) shows the activated state with P-selectin expressed on the endothelium, P-selectin is released from the Weibel-Palade body in endothelial cells. Expression is induced by hypoxia, free radicals, histamine and thrombin. In c) the leucocyte has grabbed on to the endothelium with binding of sialyated Lewis to P-Selectin. The binding is not very tight as the leucocyte may pop off again with the appearance of rolling on microscopy.

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 4. 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.