Rolling

When it contacts the endothelium, the leukocyte is still moving rapidly relative to the endothelium. In order to slow it down, surface adhesion molecules known as selectins engage upon contact. Selectins are glycoproteins that extend from the cell surface, have high mobility, and are able to rapidly bind to counter-receptors on the other cell. The binding is relatively weak, and the bond can quickly dissociate under applied force. But repeated selectin binding and breaking results in "rolling" of the cell along the endothelial wall and, most importantly, a slowing of its motion.

The most important selectins identified to date are E-, P-, and L- selectin (Table I). E- and P-selectin are expressed on endothelial cells, and L-selectin on leukocytes. Selectins bind to sialylated, fucosylated tetrasaccharide sialyl-LewisX structures. These adhesion molecules are located on microvilli, small protuberances of 300 to 700 nm on the cell surface, whereas their counterparts on the endothelial wall lie within the glycocalyx layer, which extends 50 to 500 nm above the endothelial plasma membrane. It is thought that this arrangement allows penetration of the microvilli into the negatively charged glycocalyx of the endothelium, facilitating adhesion molecule binding.

Mathematical models of cell rolling have characterized the kinetics of single adhesive bonds and the forces exerted on rolling leukocytes by the blood cells. Once rolling is achieved, the RBCs near the plasma-rich zone encourage the continued rolling of the leukocyte, adding a normal force component and torque.

Probably the most important tool in the study of cell rolling has been the parallel-plate flow chamber. This device allows direct observation of interactions between cells in a flowing fluid and a surface, which is usually coated with counter-receptors or endothelial cells. The forces experienced by cells at the wall can be calculated and varied to mimic adhesion in large and small vessels. Most importantly, this device allows observations under dynamic conditions. This is useful because many of the molecular bonds formed during leukocyte adhesion behave differently depending on the speed of the cell and the force applied. For this reason, selectin molecules could not have been characterized in static adhesion assays.

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Essentials of Human Physiology

Essentials of Human Physiology

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