Leukocyte Migration and Inflammation CHAPTER 15 347 Chemokine receptor FIGURE Chemokines signal through re Ca2+ ceptors coupled with heterotrimeric large G pro- channels teins. Binding of a chemokine to its receptor activates many signal-transduction pathways, re- sulting in a variety of modifications in the physic Adenylyl protein ogy of the target cell. If the signal-transduction PLCB pathway is not known or incompletely worked out, dashed lines and question marks are used DAG here to represent probable pathways. /Adapted from premack et al 1996. Nature Medicine PKC 2:174 CAMP Actin polymerizat Adhesion Cytoskeletal Differentiation Chemotaxis teins(Figure 15-8). Dramatic changes are effected by the Chemokine-Receptor Profiles Mediate chemokine-initiated activation of these signal transduction Leukocyte Activity pathways. Within seconds, the addition of an appropriate chemokine to leukocytes causes abrupt and extensive changes Among major populations of human leukocytes, neutrophils in shape, the promotion of greater adhesiveness to endothe- express CXCR1, 2, and-4: eosinophils have CCRl and CCR3 lial walls by activation of leukocyte integrins, and the gener-(Figure 15-9). While resting naive t cells display few types of ation of microbicidal oxygen radicals in phagocytes. These chemokine receptors, some activated T cells have CCrl, -2 ignal-transduction pathways promote other changes such 3, and-5, CXCR3 and-4, and possibly others. Clearly, a the release of granular contents, proteases in neutrophils and cell can respond to a chemokine only if it possesses a receptor macrophages, histamine from basophils, and cytotoxic pro- that recognizes it. Consequently, differences in the expression teins from eosinophils of chemokine receptors by leukocytes coupled with the N CCRI NU CXRI IL-2 Activation HNCCR2 / CXR2 NUL CCR3 nU CXR3 NL CcR4 U CXRA Activated Tlymph URE 15-9 Patterns of expression of some principal chemokine est variety of chemokine receptors has been observed on activated tors on different classes of human leukocytes. So far the great- T lymphocytes. /Adapted from M. Baggiolin, 1998, Nature 392: 565.teins (Figure 15-8). Dramatic changes are effected by the chemokine-initiated activation of these signal transduction pathways. Within seconds, the addition of an appropriate chemokine to leukocytes causes abrupt and extensive changes in shape, the promotion of greater adhesiveness to endothe￾lial walls by activation of leukocyte integrins, and the gener￾ation of microbicidal oxygen radicals in phagocytes. These signal-transduction pathways promote other changes such as the release of granular contents, proteases in neutrophils and macrophages, histamine from basophils, and cytotoxic pro￾teins from eosinophils. Chemokine-Receptor Profiles Mediate Leukocyte Activity Among major populations of human leukocytes, neutrophils express CXCR1, -2, and -4; eosinophils have CCR1 and CCR3 (Figure 15-9). While resting naive T cells display few types of chemokine receptors, some activated T cells have CCR1, -2, -3, and -5, CXCR3 and -4, and possibly others. Clearly, a cell can respond to a chemokine only if it possesses a receptor that recognizes it. Consequently, differences in the expression of chemokine receptors by leukocytes coupled with the Leukocyte Migration and Inflammation CHAPTER 15 347 α β γ Differentiation, proliferation Cytoskeletal rearrangement Adhesion Chemotaxis ? Ras Ca2+ channels Chemokine receptor ? ? cAMP Adenylyl cyclase G protein PLCβ2 IP3 DAG Ca2+ PKC Actin polymerization Neutrophil Basophil Activation T lymphocyte Resting Activated IL-2 CCR1 Eosinophil Monocyte CCR2 CCR3 CCR4 CXR1 CXR2 CXR3 CXR4 FIGURE 15-8 Chemokines signal through re￾ceptors coupled with heterotrimeric large G pro￾teins. Binding of a chemokine to its receptor activates many signal-transduction pathways, re￾sulting in a variety of modifications in the physiol￾ogy of the target cell. If the signal-transduction pathway is not known or incompletely worked out, dashed lines and question marks are used here to represent probable pathways. [Adapted from Premack et al., 1996, Nature Medicine 2:1174.] FIGURE 15-9 Patterns of expression of some principal chemokine receptors on different classes of human leukocytes. So far the great￾est variety of chemokine receptors has been observed on activated T lymphocytes. [Adapted from M. Baggiolini, 1998, Nature 392:565.]