THE 2 POLES OF THE LYMPHOCYTE - SPECIALIZED CELL COMPARTMENTS FOR MIGRATION AND RECRUITMENT

Chemotaxis, the directed migration of leukocytes towards a chemoattrac tant gradient, is a key phenomenon in the immune response. During lymp hocyte-endothelial and extracellular matrix interactions, chemokines i nduce the polarization of T lymphocytes, with generation of specialize d cell compartments. The chemokine receptors involved in detection of the chemoattractant gradients concentrate at the leading edge (advanci ng front or anterior pole) of the cell. The adhesion molecules ICAM-1, -3, CD44 and CD43 redistribute to the uropod, an appendage at the pos terior pole of migrating T lymphocyte that protrudes from the contact area with endothelial or extracellular matrix substrates. Whereas chem okine receptors sense the direction of migration, the uropod is involv ed in the recruitment of bystander leukocytes through LFA-1/ICAM-depen dent cell-cell interactions. While beta-actin concentrates preferentia lly at the cell's leading edge, the motor protein myosin II and a micr otubule organizing center (MTOC) are packed in the uropod, The actin-b inding protein moesin, which belongs to the ERM family of ezrin, radix in and moesin, redistributes to the distal portion of uropods and phys ically interacts with ICAM-3, CD44 and CD43, thus acting as a physical link between the membrane molecules and the actin cytoskeleton. Moreo ver, the moesin-ICAM-3 association correlates with the degree of cell polarity. The redistribution of the chemokine receptors and adhesion m olecules to opposite poles of the cell in response to a chemoattractan t gradient may guide cell migration and cell-cell interactions during lymphoid cell trafficking in immune and inflammatory responses.