Mature dendritic cells respond to SDF-1, but not to several beta-chemokines.
Immature dendritic cells (DCs) are highly motile, but after differentiation they stop migration. Chemokines are chemotactic cytokines that direct leukocyte trafficking, therefore we looked for the expression and function of chemokine receptors in immature and mature DCs. As a model, we used the human DCs that develop from CD14+ peripheral blood monocytes cultured with GM-CSF and IL-4. After 6-7 days in culture, these cells have the characteristics of immature DCs, but can be induced to mature further by inflammatory stimuli or by monocyte conditioned medium (MCM). Immature DCs express mRNA for CXCR4, CCR3 and CCR5. The receptors are expressed on the cell surface, as assessed with monoclonal antibodies, and are functional (with the exception of CCR3) as assessed by CA++ mobilization in response to specific chemokines. Further differentiation and maturation of DC in MCM causes a downregulation of expression and function of the beta-chemokine receptors, while CXCR4 still remains, and signals a calcium flux on mature DCs. We argue that the downregulation of beta-chemokine receptors during maturation helps to stop DC movement after T cells have been identified in lymphoid organs or at sites of delayed-type hypersensitivity.
Delgado
E
E
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY, USA.
Finkel
V
V
Baggiolini
M
M
Mackay
C R
CR
Steinman
R M
RM
Granelli-Piperno
A
A
D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000378:metabolism* / Q000494:pharmacology; D019743:Chemokines, CXC / Q000378:metabolism* / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
C515334:CCR2 protein, human; C515350:CCR3 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002118:Calcium