Chemotaxis of human monocyte-derived dendritic cells to complement component C1q is mediated by the receptors gC1qR and cC1qR.
Dendritic cells (DCs) are recruited to inflammatory sites where they phagocytose and process antigens for subsequent presentation to the T lymphocytes in the lymphoid tissue. Several leukocyte chemoattractants and their specific receptors have been shown to induce the migration of DC. The complement protein C1q has multiple immune functions including acting as a chemoattractant for neutrophils, eosinophils and mast cells. Therefore, the objective of this study was to determine if soluble C1q can induce chemotaxis of DC. Culturing cells in GM-CSF and IL-4 for 5 to 7 days generated human monocyte-derived DCs. In addition, LPS was added from day 5 to 7 to induce DC maturation. Cells were classified as either immature or mature DC by assessing the cell surface markers by flow cytometry, phagocytosis of dextran-FITC and T cell proliferation in an allogenic MLR. Immature DCs express the C1q receptors (C1qR), gC1qR and cC1qR/CR and, accordingly, display a vigorous migratory response to soluble C1q with maximal cell movement observed at 10-50nM. In contrast, mature DCs neither express C1qR nor do move to a gradient of soluble C1q. Varying the concentration gradient of C1q (checkerboard assay) showed that the protein largely induces a chemotactic response. Finally, blocking gC1qR and cC1qR/CR by using specific antibodies abolished the chemotactic response to C1q but had no effect on a different chemoattractant C5a. These results clearly demonstrate that C1q functions as a chemotactic factor for immature DC, and migration is mediated through ligation of both gC1qR and cC1qR/CR.
Vegh
Zsuzsa
Z
Department of Medicine, Stony Brook University School of Medicine, Stony Brook, NY 11794-8161, USA.
Kew
Richard R
RR
Gruber
Barry L
BL
Ghebrehiwet
Berhane
B
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D037282:Calreticulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002454:Cell Differentiation; D002462:Cell Membrane / Q000276:immunology; D002630:Chemotactic Factors / Q000378:metabolism / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology*; D015922:Complement C1q / Q000378:metabolism* / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010641:Phenotype; D011817:Rabbits; D011951:Receptors, Complement / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000906:Antibodies; C087299:C1QBP protein, human; D037282:Calreticulin; D002352:Carrier Proteins; D002630:Chemotactic Factors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D015922:Complement C1q