Margination

The first step in leukocyte adhesion is margination—the movement of the flowing cell toward the vessel wall (Figure 1). To understand this process, we have to consider the fluid dynamics of blood. The importance of blood rheology in leukocyte adhesion illustrated the fact that in the absence of red blood cells (RBCs), leukocytes only rarely contact the vessel wall and adhere.

Red blood cells constitute approximately 40 percent of the volume of blood. There are far fewer circulating leukocytes (approximately 1,000 RBCs for every leukocyte). So blood is a dense particulate suspension of RBCs, and this imparts unique fluid dynamics. In the years 1917-1938, Robin Fahraeus pioneered the study of blood as a flowing fluid. Among other things, he studied the decrease in viscosity as blood enters smaller vessels, known as the Fahraeus-Lindqvist effect. This occurs due to the formation

Figure 1 Leukocyte adhesion in a postcapillary venule. Leukocytes flowing in a dense suspension of RBCs first marginate toward the vessel wall, influenced by vessel geometry and the forces exerted by passing RBCs. Upon contact with the wall, selectin binding can occur, resulting in slowing of the cell velocity and commencement of rolling along the endothelium. If activation of the leukocyte and endothelium are sufficient, firm integrin binding can take over, and the cell stops rolling. Eventually, this cell will extravasate into the tissue to carry out its immune function. Secondary capture can occur downstream of the adherent leukocyte to amplify the recruitment of cells. (see color insert)

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arrest firm adhesion margination

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Figure 1 Leukocyte adhesion in a postcapillary venule. Leukocytes flowing in a dense suspension of RBCs first marginate toward the vessel wall, influenced by vessel geometry and the forces exerted by passing RBCs. Upon contact with the wall, selectin binding can occur, resulting in slowing of the cell velocity and commencement of rolling along the endothelium. If activation of the leukocyte and endothelium are sufficient, firm integrin binding can take over, and the cell stops rolling. Eventually, this cell will extravasate into the tissue to carry out its immune function. Secondary capture can occur downstream of the adherent leukocyte to amplify the recruitment of cells. (see color insert)

selectin binding cytoskeleton integrin binding selectin binding cytoskeleton integrin binding of a plasma-rich zone near the vessel wall and an enrichment of the RBCs near the center.

This is important because in flowing blood, leukocyte dispersion due to collisions with RBCs can force them toward the wall. This causes the leukocytes to travel preferentially in the plasma-rich zone in vessels larger than 30 mm, increasing the probability of contact with the endothelium.

The seminal studies in this area were performed in the Goldsmith laboratory using capillary tubes and sophisticated imaging techniques to track cell trajectories with high precision. Elegant mathematical analyses of particulate flow have also advanced the field (see, for example, Ref. [1]).

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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