Mechanical and biochemical aspects of leukocyte interactions with model vessel walls.

Leukocytes in flowing blood are continually undergoing collisions with the blood vessel walls. Whether these collisions result in adherence depends on a delicate balance between the fluid mechanical drag force, which tends to dislodge the PMNL, and the adhesive force generated at the area of contact with the endothelium. Local blood flow rate controls the first of these forces, with the important parameter being the velocity gradient at the wall (wall shear rate). The detailed morphology of the endothelial cell and the PMNL upon collision and the biochemical state of these cells determine the adhesive force, because this force is a product of the strength of interaction times the area of contact. If a leukocyte flattens out or spreads on the vessel wall surface, it will reduce the hydrodynamic drag and increase the area of contact, leading to a more stable adhesion. In the normal circulation, a significant fraction of the PMNL appear to be attached to the endothelium, particularly in the low flow venules. This leukocyte fraction is what hematology texts refer to as the marginal pool. The adherent PMNL are a dynamic population in the sense that some return to the circulation, some move through the endothelial cell mono-layer into the extravascular space, and others remain "attached" to the endothelial cells but roll along the surface in the flow direction. An equilibrium number is maintained under normal conditions by recruitment from the circulating pool. Increased blood flow rate will increase the hydrodynamic force, tending to dislodge the PMNL, but will also (at least in large vessels) increase the number of collisions of circulating PMNL with the vessel wall by increasing the effective "diffusion" coefficient of the leukocyte. Thus if one studied the kinetics of PMNL adhesion on an initially clean endothelial monolayer surface under flow, increasing the whole blood flow rate would probably increase in initial rate of attachment but may decrease the equilibrium number of adherent leukocytes (Fig. 5). The degree of cooperation in vivo between PMNL and endothelial cells required to enable the leukocytes to perform their bactericidal functions is fascinating. This type of interdependency also appears to be necessary in the inflammatory response [Wedmore and Williams, 1981]. Fluid mechanical forces in addition to biochemical events are crucial in regulating these interaction processes in vivo. In vitro models for examining PMNL adhesion should include control of the local fluid mechanics.(ABSTRACT TRUNCATED AT 400 WORDS)