PSGL-1 function in immunity and steady state homeostasis
| Autor: | Klaus Gossens, Wooseok Seo, Silvia Naus, Krystle M. Veerman, Douglas A. Carlow, Hermann J. Ziltener |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Chemokine
Glycosylation T-Lymphocytes Immunology Leukocyte Rolling Cell Movement Transferases Leukocyte Trafficking Animals Homeostasis Humans Immunology and Allergy Membrane Glycoproteins integumentary system biology Cell adhesion molecule Chemotaxis Hematopoietic Stem Cells Cell biology Hyaluronan Receptors Selectins biology.protein P-selectin glycoprotein ligand-1 Selectin Signal Transduction Homing (hematopoietic) |
| Zdroj: | Immunological Reviews. 230:75-96 |
| ISSN: | 1600-065X 0105-2896 |
| Popis: | The substantial importance of P-selectin glycoprotein ligand 1 (PSGL-1) in leukocyte trafficking has continued to emerge beyond its initial identification as a selectin ligand. PSGL-1 seemed to be a relatively simple molecule with an extracellular mucin domain extended as a flexible rod, teleologically consistent with its primary role in tethering leukocytes to endothelial selectins. The rolling interaction between leukocyte and endothelium mediated by this selectin-PSGL-1 interaction requires branched O-glycan extensions on specific PSGL-1 amino acid residues. In some cells, such as neutrophils, the glycosyltransferases involved in formation of the O-glycans are constitutively expressed, while in other cells, such as T cells, they are expressed only after appropriate activation. Thus, PSGL-1 supports leukocyte recruitment in both innate and adaptive arms of the immune response. A complex array of amino acids within the selectins engage multiple sugar residues of the branched O-glycans on PSGL-1 and provide the molecular interactions responsible for the velcro-like catch bonds that support leukocyte rolling. Such binding of PSGL-1 can also induce signaling events that influence cell phenotype and function. Scrutiny of PSGL-1 has revealed a better understanding of how it performs as a selectin ligand and yielded unexpected insights that extend its scope from supporting leukocyte rolling in inflammatory settings to homeostasis including stem cell homing to the thymus and mature T-cell homing to secondary lymphoid organs. PSGL-1 has been found to bind homeostatic chemokines CCL19 and CCL21 and to support the chemotactic response to these chemokines. Surprisingly, the O-glycan modifications of PSGL-1 that support rolling mediated by selectins in inflammatory conditions interfere with PSGL-1 binding to homeostatic chemokines and thereby limit responsiveness to the chemotactic cues used in steady state T-cell traffic. The multi-level influence of PSGL-1 on cell traffic in both inflammatory and steady state settings is therefore substantially determined by the orchestrated addition of O-glycans. However, central as specific O-glycosylation is to PSGL-1 function, in vivo regulation of PSGL-1 glycosylation in T cells remains poorly understood. It is our purpose herein to review what is known, and not known, of PSGL-1 glycosylation and to update understanding of PSGL-1 functional scope. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|