Multistep paradigm for leukocyte recruitment.
(a) Model of a post-capillary venule illustrating the four steps of leukocyte recruitment. These are (1) initial attachment (2) low-velocity rolling (3) arrest and activation of leukocyte integrin via locally expressed chemokines and (4) transmigration. (b) Fluid shear stress. In small venules, flow has been calculated as laminar shear stress with a parabolic velocity profile (minimum velocity at the vessel wall, maximum at the center line of the vessel). Fluid shear stress also can act directly on endothelial cells and T cells. (EC, endothelial cell; BM, basement membrane.) (Reprinted with permission from Alper, J. Searching for medicine's sweet spot. Science 291, 2338−2243 (2001).). Copyright American Association for the Advancement of Science. Original illustration by C. Cain, redrawn by B. Crimi.)