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 support 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, IFN-alpha, Dexamethasone), which 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 to be not 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 immature 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
Department of Medicine, Division of Medical Oncology, The Cancer Center of Long Island, State University of New York, Stony Brook, NY, USA.
Goyarts
Earl C
EC
Rozengarten
Kimberly
K
Mazumder
Amitabha
A
Ghebrehiwet
Berhane
B
D037282:Calreticulin / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D015922:Complement C1q / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
C087299:C1QBP protein, human; D037282:Calreticulin; D002352:Carrier Proteins; D016207:Cytokines; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D011951:Receptors, Complement; C032402:complement 1q receptor; D003907:Dexamethasone; D015922:Complement C1q