Human plasmacytoid dendritic cells express an atrial natriuretic peptide receptor, guanylyl cyclase-A.
Atrial natriuretic peptide is a cardiovascular hormone secreted mainly by the cardiac atria and regulates the volume-pressure homeostasis. The action of ANP is mediated by GC-A. We previously reported that human monocyte-derived dendritic cells express GC-A and respond to ANP with polarization toward a Th2-inducing phenotype. In the present study, we explored the possibility that pDC are subjected to immunoregulation via the ANP/GC-A system. We examined GC-A expression on blood pDC and found that GC-A was not expressed on fresh pDC but was induced after stimulation with CpG-oligodeoxynucleotide AAC-30, IL-3, or interleukin-3 plus CD40 ligand. Activated pDC responded to ANP with an increase in cGMP production, indicating that GC-A expressed on pDC was functional. We investigated whether tonsillar pDC express GC-A by immunohistochemistry and immunofluorescence staining. We found that GC-A(+) HLA-DR(+) cells were present in the T-cell areas and the perivascular areas. Flow cytometric analysis with tonsillar cells confirmed that lineage(-) CD123(high) pDC express GC-A. These results indicate that the ANP/GC-A system is involved in immune regulation through pDC in secondary lymphoid organs.
Morita
Rimpei
R
Department of Hematology and Oncology, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Fujita
Tomoko
T
Uchiyama
Takashi
T
Hori
Toshiyuki
T
D009320:Atrial Natriuretic Factor / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D006162:Guanylate Cyclase / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology*; D017461:Receptors, Atrial Natriuretic Factor / Q000276:immunology / Q000378:metabolism*
D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D006152:Cyclic GMP