Differential responsiveness to constitutive vs. inducible chemokines of immature and mature mouse dendritic cells.
Upon exposure to immune or inflammatory stimuli, dendritic cells (DC) migrate from peripheral tissues to lymphoid organs, where they present antigen. The molecular basis for the peculiar trafficking properties of DC is largely unknown. In this study, mouse DC were generated from CD34+ bone marrow precursors and cultured with granulocyte-macrophage-CSF and Flt3 ligand for 9 days. Chemokines active on immature DC include MIP1alpha, RANTES, MIP1beta, MCP-1, MCP-3, and the constitutively expressed SDF1, MDC, and ELC. TNF-alpha-induced DC maturation caused reduction of migration to inducible chemokines (MIP1alpha, RANTES, MIP1beta, MCP-1, and MCP-3) and increased migration to SDF1, MDC, and ELC. Similar results were obtained by CD40 ligation or culture in the presence of bacterial lipopolysaccharide. TNF-alpha down-regulated CC chemokine receptor (CCR)1, CCR2, and CCR5 and up-regulated CCR7 mRNA levels, in agreement with functional data. This study shows that selective responsiveness of mature and immature DC to inducible vs. constitutively produced chemokines can contribute to the regulated trafficking of DC.
Vecchi
A
A
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. VECCHI@IRFMN.MNEGRI.IT
Massimiliano
L
L
Ramponi
S
S
Luini
W
W
Bernasconi
S
S
Bonecchi
R
R
Allavena
P
P
Parmentier
M
M
Mantovani
A
A
Sozzani
S
S
D000818:Animals; D023201:CD40 Ligand; D054415:Chemokine CCL19; D018932:Chemokine CCL2 / Q000494:pharmacology; D054422:Chemokine CCL22; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology; D054410:Chemokine CCL7; D054377:Chemokine CXCL12; D018925:Chemokines / Q000494:pharmacology*; D019742:Chemokines, CC / Q000494:pharmacology; D019743:Chemokines, CXC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects*; D016207:Cytokines; D003713:Dendritic Cells / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA; D018945:Monocyte Chemoattractant Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
C515461:Ccl19 protein, mouse; C515483:Ccl22 protein, mouse; C515451:Ccl7 protein, mouse; C515301:Ccr1 protein, mouse; C515335:Ccr2 protein, mouse; C515371:Ccr7 protein, mouse; D054415:Chemokine CCL19; D018932:Chemokine CCL2; D054422:Chemokine CCL22; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D054377:Chemokine CXCL12; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D054389:Receptors, CCR1; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein; D023201:CD40 Ligand; D016178:Granulocyte-Macrophage Colony-Stimulating Factor