Differential regulation of responsiveness to fMLP and C5a upon dendritic cell maturation: correlation with receptor expression.
The trafficking of immature and mature dendritic cells (DCs) to different anatomical sites in vivo is critical for fulfilling their roles in the induction of Ag-specific immune responses. Although this process is complex and regulated by many mediators, the capacity of DCs to migrate is predominantly dependent on the expression of particular chemotactic receptors on the surface of DCs that enable them to move along chemotactic gradients formed by the corresponding chemokines and/or classical chemoattractants. Here we show that immature DCs (iDCs) respond to both fMLP and C5a as determined by chemotaxis and Ca2+ mobilization, whereas mature DCs (mDCs) respond to C5a, but not fMLP. Additionally, iDCs express the receptors for both fMLP and C5a at mRNA and protein levels. Upon maturation of DCs, fMLP receptor expression is almost completely absent, whereas C5a receptor mRNA and protein expression is maintained. Concomitantly, mDCs migrate chemotactically and mobilize intracellular Ca2+ in response to C5a, but not fMLP. Thus the interaction between C5a and its receptor is likely involved in the regulation of trafficking of both iDCs and mDCs, whereas fMLP mobilizes only iDCs. The differential responsiveness to fMLP and C5a of iDCs and mDCs suggests that they play different roles in the initiation of immune responses.
Yang
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D
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, Science Applications International Corp.-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, National Institutes of Health, MD 21702-1201, USA.
Chen
Q
Q
Stoll
S
S
Chen
X
X
Howard
O M
OM
Oppenheim
J J
JJ
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand; D002454:Cell Differentiation / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D015936:Complement C5a / Q000276:immunology* / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology* / Q000378:metabolism*; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000096:biosynthesis*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D018000:Receptors, Peptide / Q000096:biosynthesis*; D013997:Time Factors
D015703:Antigens, CD; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D023201:CD40 Ligand; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a