Human dendritic cells express functional formyl peptide receptor-like-2 (FPRL2) throughout maturation.
Immature and mature dendritic cells (iDC and mDC, respectively) migrate to different anatomical sites, e.g., sites of antigen (Ag) deposition and secondary lymphoid organs, respectively, to fulfill their roles in the induction of primary, Ag-specific immune responses. The trafficking pattern of iDC and mDC is based on their expression of functional chemotactic receptors and the in vivo sites expressing the corresponding ligands including chemokines and/or classical chemoattractants. In this study, we have evaluated the expression of the formyl peptide receptor like-2 (FPRL2) by human iDC and mDC. We show that iDC respond chemotactically and by Ca(2+) mobilization to N-formyl-Met-Leu-Phe and a recently identified synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), whereas mDC derived from the same donor only respond to WKYMVm. Furthermore, iDC and mDC express FPRL2 mRNA and protein. As mDC do not express any other members of the human FPR subfamily, FPRL2 expressed by DC must be functional and mediate the effect of WKYMVm on DC. Indeed, treatment of iDC and mDC with WKYMVm induces the internalization of FPRL2. Thus, human myeloid DC express functional FPRL2 and maintain its expression even after maturation, suggesting that the interaction of FPRL2 and its endogenous ligand(s) may be involved in regulating DC trafficking during Ag uptake and processing in the periphery as well as the T cell-stimulating phase of the immune responses.
Yang
De
D
Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Maryland 21702-1201, USA.
Chen
Qian
Q
Gertz
Barry
B
He
Rong
R
Phulsuksombati
Michele
M
Ye
Richard D
RD
Oppenheim
Joost J
JJ
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D020013:Calcium Signaling / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D018000:Receptors, Peptide / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D008024:Ligands; D008070:Lipopolysaccharides; C408903:MMK-1 peptide; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; C113617:Trp-Lys-Tyr-Met-Val-Met; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor