title: Migration of human blood dendritic cells across endothelial cell monolayers: adhesion molecules and chemokines involved in subset-specific transmigration.
abstract: Distinct subsets of dendritic cells (DCs) are present in blood, probably "en route" to different tissues. We have investigated the chemokines and adhesion molecules involved in the migration of myeloid (CD11c(+)) and plasmacytoid (CD123(+)) human peripheral blood DCs across vascular endothelium. Among blood DCs, the CD11c(+) subset vigorously migrated across endothelium in the absence of any chemotactic stimuli, whereas spontaneous migration of CD123(+) DCs was limited. In bare cell migration assays, myeloid DCs responded with great potency to several inflammatory and homeostatic chemokines, whereas plasmacytoid DCs responded poorly to all chemokines tested. In contrast, the presence of endothelium greatly favored transmigration of plasmacytoid DCs in response to CXCL12 (stromal cell-derived factor-1) and CCL5 (regulated on activation, normal T expressed and secreted). Myeloid DCs exhibited a very potent transendothelial migration in response to CXCL12, CCL5, and CCL2 (monocyte chemoattractant protein-1). Furthermore, we explored whether blood DCs acutely switch their pattern of migration to the lymph node-derived chemokine CCL21 (secondary lymphoid-tissue chemokine) in response to microbial stimuli [viral double-stranded (ds)RNA or bacterial CpG-DNA]. A synthetic dsRNA rapidly enhanced the response of CD11c(+) DCs to CCL21, whereas a longer stimulation with CpG-DNA was needed to trigger CD123(+) DCs responsive to CCL21. Use of blocking monoclonal antibodies to adhesion molecules revealed that both DC subsets used platelet endothelial cell adhesion molecule-1 to move across activated endothelium. CD123(+) DCs required beta(2) and beta(1) integrins to transmigrate, whereas CD11c(+) DCs may use integrin-independent mechanisms to migrate across activated endothelium.
authors.affiliation: Servicio de Inmunología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: de la Rosa
authors.forename: Natividad
authors.initials: N
authors.lastname: Longo
authors.forename: Jose L
authors.initials: JL
authors.lastname: Rodríguez-Fernández
authors.forename: Amaya
authors.initials: A
authors.lastname: Puig-Kroger
authors.forename: Alfonso
authors.initials: A
authors.lastname: Pineda
authors.forename: Angel L
authors.initials: AL
authors.lastname: Corbí
authors.forename: Paloma
authors.initials: P
authors.lastname: Sánchez-Mateos
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D039521:CD11c Antigen / Q000032:analysis; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D054413:Chemokine CCL11; D054415:Chemokine CCL19; D018932:Chemokine CCL2 / Q000494:pharmacology; D054421:Chemokine CCL21; D018946:Chemokine CCL5 / Q000494:pharmacology; D054410:Chemokine CCL7; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054377:Chemokine CXCL12; D054370:Chemokine CXCL9; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D019742:Chemokines, CC / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D018899:CpG Islands / Q000276:immunology; D016207:Cytokines; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D053650:Interleukin-3 Receptor alpha Subunit; D018945:Monocyte Chemoattractant Proteins / Q000494:pharmacology; D022423:Myeloid Cells / Q000166:cytology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology; D012330:RNA, Double-Stranded / Q000138:chemical synthesis / Q000494:pharmacology; D016185:Receptors, Interleukin-3 / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; C515456:CCL11 protein, human; C099677:CCL13 protein, human; C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515450:CCL7 protein, human; D039521:CD11c Antigen; D018821:CD18 Antigens; C515202:CXCL11 protein, human; C515255:CXCL12 protein, human; C080810:CXCL9 protein, human; D015815:Cell Adhesion Molecules; D054413:Chemokine CCL11; D054415:Chemokine CCL19; D018932:Chemokine CCL2; D054421:Chemokine CCL21; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054377:Chemokine CXCL12; D054370:Chemokine CXCL9; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; C115022:IL3RA protein, human; D019012:Integrin beta1; D036341:Intercellular Signaling Peptides and Proteins; D053650:Interleukin-3 Receptor alpha Subunit; D018945:Monocyte Chemoattractant Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012330:RNA, Double-Stranded; D016185:Receptors, Interleukin-3; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1