CCR5 expression on monocytes and T cells: modulation by transmigration across the blood-brain barrier in vitro.

Abstract

Observational studies in multiple sclerosis (MS) demonstrated altered expression of chemokine receptors (CkRs) on comparable populations of mononuclear cells (e.g. CD4(+)/CD45RO(+) T-cells) in brain sections compared with blood. These findings raised questions about the regulation of CkRs on trafficking cells. Regulatory processes for CkRs are complex: examples include down-regulation following ligand engagement during migration and either up- or down-regulation following activation. Additionally, CkRs that mediate transmigration without being down-regulated will be selectively enriched on migrating cells in the inflammatory site. Finally, CkRs may act as functionally neutral markers of activated cells capable of undergoing transmigration. Clarifying CkR regulation may aid in the selection and application of antagonists for treating neuroinflammation. Mechanisms of receptor regulation during transmigration cannot be studied by descriptive methods. We evaluated CCR5 expression on CD14(+) monocytes and CD3(+) T-cells following CCL5-driven transmigration through an in vitro blood-brain barrier (IVBBB), as both T-cells and monocytes in MS lesions express CCR5. CCR5 expression was augmented on non-migrating CD14(+) but not CD3(+) cells, suggesting selective activation of monocytes by incubation in contact with endothelial cells. As proposed from observational studies, CCR5 was enriched on monocytes that migrated spontaneously in the absence of exogenous chemokine. Addition of the CCR5 ligand CCL5 to the lower chamber led to enhanced CD3(+) T-cell migration. Interestingly, CCR5 was down-regulated on both CD14(+) monocytes and CD3(+) T cells during CCL5-driven migration. These results are distinct from those obtained in comparable studies of CCR2 and CXCR3, suggesting that the specifics for CkR expression should be studied for individual receptors on each leukocyte subpopulation during the design of strategies for pharmacological blockade in neuroinflammation.

• Authors: Eroboghene E Ubogu, Melissa K Callahan, Barbara H Tucky, Richard M Ransohoff
• Journal: Cellular immunology (Cell Immunol) Vol. 243 Issue 1 Pg. 19-29 (Sep 2006) ISSN: 0008-8749 [Print] Netherlands
• PMID: 17257590 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CCL5 protein, human
• CD3 Complex
• Chemokine CCL5
• Chemokines, CC
• Lipopolysaccharide Receptors
• Receptors, CCR5

Topics

• Blood-Brain Barrier (physiology)
• CD3 Complex (metabolism)
• Cell Movement
• Cells, Cultured
• Chemokine CCL5
• Chemokines, CC (pharmacology)
• Down-Regulation
• Endothelial Cells (physiology)
• Humans
• Lipopolysaccharide Receptors (metabolism)
• Monocytes (drug effects, metabolism)
• Receptors, CCR5 (metabolism)
• T-Lymphocytes (drug effects, metabolism, physiology)