Leukocyte Migration and Inflammation CHAPTER 15 341 Activation Arrest/ Transendothelial FIGURE 15-3(a)The four sequential adhesion migration but overlapping steps in neutrophil ex- travasation.(b)Cell-adhesion molecules and chemokines involved in the first three Endothelium ③雪 like CAMs. a chemokine such as IL-8 ther binds to a G-protein-linked receptor on the neutrophil, triggering an activating sig- nal. This signal induces a conformational change in the integrin molecules, enabling em to adhere firmly to Ig-superfamily utrop molecules on the endothelium Chemokine or iter Mucin-Ii E-selectin O Chen 8) Step Step trophil membrane, increasing their affinity for the Ig-super- sation of lymphocytes involves interactions among a number family adhesion molecules on the endothelium. Subsequent of cell-adhesion molecules (Table 15-1). The overall process interaction between integrins and Ig-superfamily CAMs stabi- is similar to what happens during neutrophil extravasation lizes adhesion of the neutrophil to the endothelial cell, enabl- and comprises the same four stages of contact and rolling, ing the cell to adhere firmly to the endothelial cell activation, arrest and adhesion, and, finally, transendothelial Subsequently, the neutrophil migrates through the vessel migr wall into the tissues. The steps in transendothelial migration and how it is directed are still largely unknown; they may be High-Endothelial Venules Are Sites mediated by further activation by chemoattractants and sub- sequent integrin-Ig-superfamily interactions or by a separate of Lymphocyte Extravasation migration stimulus Some regions of vascular endothelium in postcapillary varlous lymphoid organs are composed of special ized cells with a plump, cuboidal ("high") shape; such re Lymphocyte Extravasation gions are called high-endothelial venules, or HEVs(Figure 5-4a, b). Their cells contrast sharply in appearance with the Various subsets of lymphocytes exhibit directed extravasa- flattened endothelial cells that line the rest of the capillary tion at inflammatory sites and secondary lymphoid organs. Each of the secondary lymphoid organ epton The recirculation of lymphocytes thus is carefully controlled of the spleen, contains HEVs. When frozen sections of lymph to ensure that appropriate populations of B and T cells are nodes, Peyers patches, or tonsils are incubated with lympho- recruited into different tissues. As with neutrophils, extrava- cytes and washed to remove unbound cells, over 85%of the Gotowww.whfreeman.com/immunology(animationtrophil membrane, increasing their affinity for the Ig-super￾family adhesion molecules on the endothelium. Subsequent interaction between integrins and Ig-superfamily CAMs stabi￾lizes adhesion of the neutrophil to the endothelial cell, enabl￾ing the cell to adhere firmly to the endothelial cell. Subsequently, the neutrophil migrates through the vessel wall into the tissues. The steps in transendothelial migration and how it is directed are still largely unknown; they may be mediated by further activation by chemoattractants and sub￾sequent integrin–Ig-superfamily interactions or by a separate migration stimulus. Lymphocyte Extravasation Various subsets of lymphocytes exhibit directed extravasa￾tion at inflammatory sites and secondary lymphoid organs. The recirculation of lymphocytes thus is carefully controlled to ensure that appropriate populations of B and T cells are recruited into different tissues. As with neutrophils, extrava￾sation of lymphocytes involves interactions among a number of cell-adhesion molecules (Table 15-1). The overall process is similar to what happens during neutrophil extravasation and comprises the same four stages of contact and rolling, activation, arrest and adhesion, and, finally, transendothelial migration. High-Endothelial Venules Are Sites of Lymphocyte Extravasation Some regions of vascular endothelium in postcapillary venules of various lymphoid organs are composed of special￾ized cells with a plump, cuboidal (“high”) shape; such re￾gions are called high-endothelial venules, or HEVs (Figure 15-4a, b). Their cells contrast sharply in appearance with the flattened endothelial cells that line the rest of the capillary. Each of the secondary lymphoid organs, with the exception of the spleen, contains HEVs. When frozen sections of lymph nodes, Peyer’s patches, or tonsils are incubated with lympho￾cytes and washed to remove unbound cells, over 85% of the Leukocyte Migration and Inflammation CHAPTER 15 341 Endothelium (a) Rolling Activation Arrest/ adhesion Transendothelial migration 1 2 3 4 (b) Step 2 Step 3 Step 1 Neutrophil Integrin Ig-superfamily E-selectin CAM Chemokine or chemoattractant receptor Mucin-like CAM Chemokine (IL-8) SS SS SS SS FIGURE 15-3 (a) The four sequential but overlapping steps in neutrophil ex￾travasation. (b) Cell-adhesion molecules and chemokines involved in the first three steps of neutrophil extravasation. Initial rolling is mediated by binding of E-selectin molecules on the vascular endothelium to sialylated carbohydrate moieties on mucin￾like CAMs. A chemokine such as IL-8 then binds to a G-protein–linked receptor on the neutrophil, triggering an activating sig￾nal. This signal induces a conformational change in the integrin molecules, enabling them to adhere firmly to Ig-superfamily molecules on the endothelium. Go to www.whfreeman.com/immunology Animation Leukocyte Extravasation