_Dr. Simon's lecture_weberrev

_Dr. Simon's lecture_weberrev - J Mol Med (2003) 81:419 DOI

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Abstract The emigration of leukocytes from the circula- tion is a critical step during immune surveillance and in- flammatory reactions and is governed by a coordinated interplay involving a spectrum of adhesion and signal molecules. As the original multistep model of leukocyte trafficking undergoes continuous revision and refine- ment, the identification of additional molecules and the emergence of novel concepts for their intricately over- lapping functions indicate that this process is still not completely understood. Early studies defining the multi- step model described the rapid transition of selectin- mediated leukocyte rolling into integrin-dependent arrest followed by transendothelial diapedesis. It has become apparent that highly specialized chemoattractive cyto- kines termed chemokines and their heptahelical receptors are involved in the emigration of leukocytes not only by inducing chemotaxis but also by regulating integrins to trigger cell arrest in shear flow. In light of the enormous- ly pleiotropic role of integrins and chemokines in verte- brate biology, this review summarizes and highlights se- lected aspects of currently evolving concepts refining the multistep model: (a) the differential activation of integrin avidity by chemokines and its implications, (b) the func- tional specialization of chemokines and their receptors in leukocyte recruitment, and (c) the multilayered molecu- lar “zipper” controlling the completion of diapedesis at interendothelial junctions. Keywords Integrins · Chemokines · Junctional adhesion molecule · Leukocyte · Emigration · Inflammation Abbreviations ARF: ADP-ribosylation factor · CCR: CC chemokine receptor · CXCR: CXC chemokine receptor · ERK: Extracellular regulated kinase · GEF: Guanine exchange factor · GRO: Growth-related oncogene · ICAM: Intercellular adhesion molecule · IL: Interleukin · JAM : Junctional adhesion molecule · LFA: Lymphocyte function-associated antigen · mAb: Monoclonal antibody · MCP: Monocyte chemotactic protein · MIP: Macrophage inflammatory protein · PECAM: Platelet-endothelial cell adhesion molecule · PH: Pleckstrin homology · PI3 - K: Phosphatidylinositol 3-OH kinase · RANTES: Regulated on activation normal T cell expressed and secreted · SDF: Stromal cell-derived factor · TEM: Transendothelial migration · TNF: Tumor necrosis factor · VCAM: Vascular cell adhesion molecule Introduction The emigration of leukocytes from the circulation is con- trolled by a coordinated interplay of multiple signal and adhesion molecules, in particular selectins, chemoattract- ants, and integrins [1, 2]. The selectin family features molecules with a N-terminal domain homologous to lec- tins, which interact with sialylated carbohydrate determi- nants, for example, on mucinlike glycoproteins and me- diate initial tethering to the vessel wall and rolling of leukocytes [1]. Chemoattractants are a diverse group of molecules which can activate heptahelical G protein cou-
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This note was uploaded on 12/30/2010 for the course PMI 285 taught by Professor Wu during the Winter '04 term at UC Davis.

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_Dr. Simon's lecture_weberrev - J Mol Med (2003) 81:419 DOI

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