title: Astrocytes produce dendritic cell-attracting chemokines in vitro and in multiple sclerosis lesions.
abstract: As a result of their close association with the blood-brain barrier, astrocytes play an important role in regulating the homing of different leukocyte subsets to the inflamed central nervous system (CNS). In this study, we investigated whether human astrocytes produce chemokines that promote the migration of myeloid dendritic cells (DCs). By reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, we show that cultured human astrocytes stimulated with interleukin-1beta and tumor necrosis factor produce CCL2, CCL3, CCL4, CCL5, CCL20, and CXCL12 that act on immature DCs, but not CCL19 and CCL21, 2 chemokines specific for mature DCs. Compared with controls, supernatants of cytokine-stimulated astrocytes are more effective in promoting the migration of immature monocyte-derived DCs (iMDDCs). Desensitization of CXCR4 (receptor for CXCL12), CCR1-3-5 (shared receptors for CCL3-4-5), and CCR6 (receptor for CCL20) on iMDDC reduces cell migration toward astrocyte supernatants, indicating that astrocytes release biologically relevant amounts of iMDDC-attracting chemokines. By immunohistochemistry, we show that CXCL12 and, to a lesser extent, CCL20 are expressed by reactive astrocytes in multiple sclerosis lesions. These data lend support to the idea that astrocyte-derived chemokines may contribute to immature DC recruitment to the inflamed CNS.
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. ambrosin@iss.it
authors.forename: Elena
authors.initials: E
authors.lastname: Ambrosini
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Remoli
authors.forename: Elena
authors.initials: E
authors.lastname: Giacomini
authors.forename: Barbara
authors.initials: B
authors.lastname: Rosicarelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Serafini
authors.forename: Roberto
authors.initials: R
authors.lastname: Lande
authors.forename: Francesca
authors.initials: F
authors.lastname: Aloisi
authors.forename: Eliana Marina
authors.initials: EM
authors.lastname: Coccia
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005333:Fetus; D005434:Flow Cytometry / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007375:Interleukin-1 / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019742:Chemokines, CC; D005904:Glial Fibrillary Acidic Protein; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule