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Activation of pertussis toxin-sensitive CXCL12 (SDF-1) receptors mediates transendothelial migration of T lymphocytes across lymph node high endothelial cells.
- Source :
-
European journal of immunology [Eur J Immunol] 2002 Mar; Vol. 32 (3), pp. 837-47. - Publication Year :
- 2002
-
Abstract
- In this study we examined the role of chemokines in regulating T lymphocyte transmigration across the lining high endothelial cells (HEC) of high endothelial venules (HEV). The roles played by CCL21 (SLC), CCL19 (MIP-3 beta, ELC) and CXCL12 (SDF-1) were assessed using an in vitro transendothelial migration culture system, which constitutively supports high levels of lymphocyte transmigration. We determined that transmigration of T lymphocytes across HEC is inhibitable by treatment of the T lymphocytes with pertussis toxin (PTX) (80% inhibition). This was attributed to blockade of Gi-protein coupled receptors of T lymphocytes, since a non-ADP-ribosylating form of PTX had no significant effect on transendothelial migration. Inhibition of Gi-protein-coupled receptors on the endothelium had no effect on T cell transmigration. Treatment of T lymphocytes with a desensitizing concentration of CXCL12 caused a 60% reduction in T lymphocyte migration across HEC, and the CXCR4 antagonist SDF-1P2G reduced transmigration by 40%. Desensitizing concentrations of CCL21 and CCL19 had no significant effects on T lymphocyte transendothelial migration. Homologous desensitization of T lymphocytes to each chemokine was confirmed in a transwell migration assay. An approximately 3-kb mRNA corresponding to rat SDF-1 beta was constitutively expressed in HEC and cell surface CXCL12 was detectable by enzyme-linked immunosorbent assay. Together, these findings support a pivotal role for HEC-expressed CXCL12 and its receptor on T cells in the regulation of T lymphocyte homing to lymph nodes.
- Subjects :
- Adenosine Diphosphate Ribose metabolism
Animals
Cells, Cultured drug effects
Chemokine CCL19
Chemokine CCL21
Chemokine CXCL12
Chemokines, CC pharmacology
Chemokines, CC physiology
Chemokines, CXC biosynthesis
Chemokines, CXC genetics
Chemokines, CXC pharmacology
Chemotaxis drug effects
Endothelium cytology
Enzyme-Linked Immunosorbent Assay
GTP-Binding Protein alpha Subunits, Gi-Go drug effects
GTP-Binding Protein alpha Subunits, Gi-Go physiology
Humans
Mice
RNA, Messenger biosynthesis
Rats
Receptors, CXCR4 antagonists & inhibitors
Receptors, Chemokine drug effects
Receptors, Chemokine physiology
Chemokines, CXC physiology
Lymph Nodes cytology
Pertussis Toxin
T-Lymphocytes drug effects
Virulence Factors, Bordetella pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2980
- Volume :
- 32
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 11870628
- Full Text :
- https://doi.org/10.1002/1521-4141(200203)32:3<837::AID-IMMU837>3.0.CO;2-Q