Celtaxsys - Biology in Reverse

Figure 2: Leukocytes must under go four adhesion steps to accumulate in a blood vessel: Tethering, Rolling, Activation and Adhesion. The predominant leukocyte-expressed trafficking molecules that participate in each step and their endothelial counter-receptors are indicated. Arrows indicate interactions of individual molecules with one or more binding partners. Leukocytes in the blood stream tether to endothelial cell ligands and roll slowly downstream. Tethering is mediated mainly by leukocyte receptors on tips of surface microvilli (L-selectin, PSGL-1 and α4 integrins). L-selectin recognizes sulfated sialyl-Lewis X (sLeX)-like sugars as well as PSGL-1 on adherent leukocytes (broken arrows). E-selectin can also interact with PSGL-1 and other sialyl-Lewis X-bearing glycoconjugates, commonly called 'CLA'. E-selectin and the α4 integrins can stabilize rolling mediated by L- and P-selectin and reduce rolling velocities. When a GPCR on a rolling cell becomes engaged by a specific chemoattractant (often a chemokine), the activating signal (red square) is transmitted intracellularly to induce rapid activation of β2 and/or α4 integrins, which assume extended conformations and bind tightly to endothelial immunoglobulin superfamily members. Prolonged ligation of L-selectin or ligands for E- and P-selectin can act in synergy with or even substitute for GPCR signals to activate β2 integrins in some settings. Image and description courtesy of Ulrich von Andrian of Harvard Medical School, a member of the Scientific Advisory Board.