Maturation-dependent expression of C1q-binding proteins on the cell surface of human monocyte-derived dendritic cells.
The expression and cell surface levels of many important receptors are dependent on the maturation stage of dendritic cells (DCs), and related to the unique function of immature and mature DCs. In this report, we show for the first time that human monocyte-derived DCs express two types of C1q-receptors, gC1qR and cC1qR. Furthermore, immature DCs secrete detectable amount of C1q into the culture supernatant. Immature DCs express higher cell surface levels of both C1qRs than mature ones, while the total C1qR protein and mRNA levels remain the same. The following experimental evidence supports this conclusion. (1) Inflammatory cytokines and LPS, which induce maturation of DCs, downregulate surface expression of both C1qR molecules. (2) Cytokines and drugs (IL-10, IFNalpha, dexamethasone) that keep DCs phenotypically and functionally immature significantly upregulate the cell surface expression of both C1qRs. (3) Neither of these treatments changed the intracellular gC1qR level nor the gC1qR mRNA levels measured by real-time RT-PCR. The elevated surface expression of C1qRs on DCs has been found not to be due to increased apoptosis or cell death as the result of DC treatment. Taken together, these data show that human monocyte-derived DCs express gC1qR and cC1qR, their expression on the cell surface is maturation dependent and imature DCs secrete C1q. These data strongly suggest the role of C1qRs in immature DC function and in the regulation of immune processes.
Vegh
Zsuzsa
Z
Division of Medical Oncology, The Department of Medicine, The Cancer Center of Long Island, Stony Brook, NY, USA.
Goyarts
Earl C
EC
Rozengarten
Kimberly
K
Mazumder
Amitabha
A
Ghebrehiwet
Berhane
B
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins; D002478:Cells, Cultured; D003470:Culture Media; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D003713:Dendritic Cells / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D007959:Lymphocyte Culture Test, Mixed; D018613:Microscopy, Confocal; D009000:Monocytes / Q000378:metabolism*; D010641:Phenotype; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000893:Anti-Inflammatory Agents; D002352:Carrier Proteins; D003470:Culture Media; D016207:Cytokines; D018076:DNA, Complementary; D007202:Indicators and Reagents; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C007105:c1q-binding proteins; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor