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PMID: 9151897 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Human macrophage-derived chemokine (MDC), a novel chemoattractant for monocytes, monocyte-derived dendritic cells, and natural killer cells.

The Journal of experimental medicine ·Vol. 185 ·No. 9 ·1997-05-05 ·Pages 1595-604

Godiska R, Chantry D, Raport CJ, Sozzani S, Allavena P, Leviten D, Mantovani A, Gray PW

Abstract

A cDNA encoding a novel human chemokine was isolated by random sequencing of cDNA clones from human monocyte-derived macrophages. This protein has been termed macrophage-derived chemokine (MDC) because it appears to be synthesized specifically by cells of the macrophage lineage. MDC has the four-cysteine motif and other highly conserved residues characteristic of CC chemokines, but it shares <35% identity with any of the known chemokines. Recombinant MDC was expressed in Chinese hamster ovary cells and purified by heparin-Sepharose chromatography. NH2-terminal sequencing and mass spectrophotometry were used to verify the NH2 terminus and molecular mass of recombinant MDC (8,081 dalton). In microchamber migration assays, monocyte-derived dendritic cells and IL-2-activated natural killer cells migrated to MDC in a dose-dependent manner, with a maximal chemotactic response at 1 ng/ml. Freshly isolated monocytes also migrated toward MDC, but with a peak response at 100 ng/ml MDC. Northern analyses indicated MDC is highly expressed in macrophages and in monocyte-derived dendritic cells, but not in monocytes, natural killer cells, or several cell lines of epithelial, endothelial, or fibroblast origin. High expression was also detected in normal thymus and less expression in lung and spleen. Unlike most other CC chemokines, MDC is encoded on human chromosome 16. MDC is thus a unique member of the CC chemokine family that may play a fundamental role in the function of dendritic cells, natural killer cells, and monocytes.

MeSH Terms
Amino Acid Sequence Chemokine CCL22 Chemokines, CC/genetics,isolation & purification Chemotaxis, Leukocyte Chromosomes, Human, Pair 16 Cloning, Molecular DNA, Complementary/genetics Dendritic Cells/physiology Gene Expression Humans Killer Cells, Natural/physiology Macrophage Inflammatory Proteins/genetics Macrophages/physiology Molecular Sequence Data Monocytes/physiology Phylogeny RNA, Messenger/genetics Sequence Alignment Sequence Homology, Nucleic Acid Tissue Distribution
Chemicals
CCL22 protein, human Chemokine CCL22 Chemokines, CC DNA, Complementary Macrophage Inflammatory Proteins RNA, Messenger
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Godiska R
Icos Corporation, Bothell, Washington 98021, USA.
Chantry D
Raport C J
Sozzani S
Allavena P
Leviten D
Mantovani A
Gray P W
References (67)
67 references, click to expand
  1. Structures of human genes coding for cytokine LD78 and their expression.
    Mol Cell Biol. 1990 Jul;10(7):3646-58 PMID: 1694014
  2. Cloning and characterization of exodus, a novel beta-chemokine.
    Blood. 1997 May 1;89(9):3315-22 PMID: 9129037
  3. Antigen uptake and presentation by dendritic leukocytes.
    Semin Immunol. 1992 Aug;4(4):227-36 PMID: 1391797
  4. New insights into the mobilization and phagocytic activity of dendritic cells.
    J Exp Med. 1996 Apr 1;183(4):1287-92 PMID: 8666885
  5. Biology and clinical relevance of human natural killer cells.
    Blood. 1990 Dec 15;76(12):2421-38 PMID: 2265240
  6. Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1(alpha), MIP-1(beta), and RANTES.
    J Leukoc Biol. 1996 Jul;60(1):147-52 PMID: 8699119
  7. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5.
    Nature. 1996 Jun 20;381(6584):667-73 PMID: 8649512
  8. A novel polypeptide secreted by activated human T lymphocytes.
    J Immunol. 1989 Nov 1;143(9):2907-16 PMID: 2809212
  9. Molecular cloning of a novel T cell-directed CC chemokine expressed in thymus by signal sequence trap using Epstein-Barr virus vector.
    J Biol Chem. 1996 Aug 30;271(35):21514-21 PMID: 8702936
  10. Monocyte chemoattractant protein-3 is a functional ligand for CC chemokine receptors 1 and 2B.
    J Biol Chem. 1995 Dec 15;270(50):29671-5 PMID: 8530354
  11. Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis.
    J Immunol. 1995 Oct 15;155(8):3877-88 PMID: 7561094
  12. Effect of gamma rays at the dihydrofolate reductase locus: deletions and inversions.
    Somat Cell Mol Genet. 1986 Nov;12(6):555-66 PMID: 3024331
  13. IL-8 induces the locomotion of human IL-2-activated natural killer cells. Involvement of a guanine nucleotide binding (Go) protein.
    J Immunol. 1993 Feb 15;150(4):1524-34 PMID: 8381837
  14. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines.
    Adv Immunol. 1994;55:97-179 PMID: 8304236
  15. Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family.
    J Exp Med. 1992 Jul 1;176(1):59-65 PMID: 1613466
  16. Alu alert.
    Nature. 1994 Oct 27;371(6500):752 PMID: 7935834
  17. Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line.
    J Exp Med. 1989 Apr 1;169(4):1485-90 PMID: 2926331
  18. Assignment of the human CC chemokine gene TARC (SCYA17) to chromosome 16q13.
    Genomics. 1997 Feb 15;40(1):211-3 PMID: 9070951
  19. Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils.
    J Exp Med. 1996 Jun 1;183(6):2437-48 PMID: 8676064
  20. Chemokine expression in murine experimental allergic encephalomyelitis.
    J Neuroimmunol. 1995 May;58(2):167-76 PMID: 7539012
  21. The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates.
    Cell. 1996 Jun 28;85(7):1135-48 PMID: 8674119
  22. A new method for predicting signal sequence cleavage sites.
    Nucleic Acids Res. 1986 Jun 11;14(11):4683-90 PMID: 3714490
  23. Cloning of a cDNA encoding chitotriosidase, a human chitinase produced by macrophages.
    J Biol Chem. 1995 Nov 3;270(44):26252-6 PMID: 7592832
  24. Molecular cloning, functional expression, and signaling characteristics of a C-C chemokine receptor.
    Cell. 1993 Feb 12;72(3):415-25 PMID: 7679328
  25. Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines.
    J Immunol. 1995 Oct 1;155(7):3292-5 PMID: 7561021
  26. Molecular cloning and functional expression of a novel CC chemokine receptor cDNA from a human basophilic cell line.
    J Biol Chem. 1995 Aug 18;270(33):19495-500 PMID: 7642634
  27. Activation of NK cells by CC chemokines. Chemotaxis, Ca2+ mobilization, and enzyme release.
    J Immunol. 1996 Jan 1;156(1):322-7 PMID: 8598480
  28. The immunologic properties of epidermal Langerhans cells as a part of the dendritic cell system.
    Springer Semin Immunopathol. 1992;13(3-4):265-79 PMID: 1411898
  29. Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha.
    J Biol Chem. 1996 Jul 19;271(29):17161-6 PMID: 8663314
  30. A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors.
    Cell. 1996 Jun 28;85(7):1149-58 PMID: 8674120
  31. Migratory Response of Human NK Cells to Monocyte-Chemotactic Proteins
    Methods. 1996 Aug;10(1):145-9 PMID: 8812655
  32. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1.
    Science. 1996 Jun 28;272(5270):1955-8 PMID: 8658171
  33. Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3.
    J Biol Chem. 1996 Mar 29;271(13):7725-30 PMID: 8631813
  34. Induction of natural killer cell migration by monocyte chemotactic protein-1, -2 and -3.
    Eur J Immunol. 1994 Dec;24(12):3233-6 PMID: 7805752
  35. Structural requirements for interleukin-8 function identified by design of analogs and CXC chemokine hybrids.
    J Biol Chem. 1994 Jun 10;269(23):16075-81 PMID: 8206907
  36. Monocyte chemoattractant protein-3, but not monocyte chemoattractant protein-2, is a functional ligand of the human monocyte chemoattractant protein-1 receptor.
    J Immunol. 1995 Jun 15;154(12):6511-7 PMID: 7759884
  37. Monocyte chemotactic protein 4 (MCP-4), a novel structural and functional analogue of MCP-3 and eotaxin.
    J Exp Med. 1996 May 1;183(5):2379-84 PMID: 8642349
  38. Identification of a major co-receptor for primary isolates of HIV-1.
    Nature. 1996 Jun 20;381(6584):661-6 PMID: 8649511
  39. HCC-1, a novel chemokine from human plasma.
    J Exp Med. 1996 Jan 1;183(1):295-9 PMID: 8551235
  40. Antagonists of monocyte chemoattractant protein 1 identified by modification of functionally critical NH2-terminal residues.
    J Exp Med. 1995 Feb 1;181(2):631-40 PMID: 7836918
  41. Overview of chemokines.
    Adv Exp Med Biol. 1993;351:183-6 PMID: 7942295
  42. Biology of the RANTES/SIS cytokine family.
    Cytokine. 1991 May;3(3):165-83 PMID: 1715772
  43. Recent advances in the study of dendritic cells and follicular dendritic cells.
    Immunol Today. 1995 Jan;16(1):2-4 PMID: 7880384
  44. C-C chemokines induce the chemotaxis of NK and IL-2-activated NK cells. Role for G proteins.
    J Immunol. 1994 Dec 1;153(11):4969-77 PMID: 7525719
  45. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.
    J Exp Med. 1994 Apr 1;179(4):1109-18 PMID: 8145033
  46. Human macrophages secret platelet-activating factor acetylhydrolase.
    J Biol Chem. 1990 Jun 15;265(17):9682-7 PMID: 2351664
  47. A human T cell-specific molecule is a member of a new gene family.
    J Immunol. 1988 Aug 1;141(3):1018-25 PMID: 2456327
  48. Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1.
    J Leukoc Biol. 1996 Jan;59(1):67-74 PMID: 8558070
  49. Oxidized LDL potentiates LPS-induced transcription of the chemokine KC gene.
    J Leukoc Biol. 1996 Jun;59(6):940-7 PMID: 8691081
  50. Dermal tumour necrosis factor-alpha induces dendritic cell migration to draining lymph nodes, and possibly provides one stimulus for Langerhans' cell migration.
    Immunology. 1992 Feb;75(2):257-63 PMID: 1551688
  51. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  52. Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and nonallergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3.
    J Immunol. 1996 Dec 15;157(12):5613-26 PMID: 8955214
  53. The dendritic cell system and its role in immunogenicity.
    Annu Rev Immunol. 1991;9:271-96 PMID: 1910679
  54. Biology of natural killer cells.
    Adv Immunol. 1989;47:187-376 PMID: 2683611
  55. Terminal differentiation surface antigens of myelomonocytic cells are expressed in human promyelocytic leukemia cells (HL60) treated with chemical inducers.
    Blood. 1981 Oct;58(4):836-43 PMID: 6944113
  56. A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes.
    J Immunol. 1989 Jan 15;142(2):679-87 PMID: 2521353
  57. Interleukin 8 is induced by cholesterol loading of macrophages and expressed by macrophage foam cells in human atheroma.
    J Biol Chem. 1996 Apr 12;271(15):8837-42 PMID: 8621523
  58. Migratory response of human natural killer cells to lymphotactin.
    Eur J Immunol. 1996 Dec;26(12):3238-41 PMID: 8977329
  59. Cloning, expression, and characterization of the human eosinophil eotaxin receptor.
    J Exp Med. 1996 May 1;183(5):2349-54 PMID: 8642344
  60. Monocyte chemotactic protein-4: tissue-specific expression and signaling through CC chemokine receptor-2.
    J Leukoc Biol. 1997 Mar;61(3):353-60 PMID: 9060459
  61. Anti-inflammatory properties of a platelet-activating factor acetylhydrolase.
    Nature. 1995 Apr 6;374(6522):549-53 PMID: 7700381
  62. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1.
    Nature. 1996 Aug 15;382(6592):635-8 PMID: 8757135
  63. Unresponsiveness of primitive chronic myeloid leukemia cells to macrophage inflammatory protein 1 alpha, an inhibitor of primitive normal hematopoietic cells.
    Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):12015-9 PMID: 8265663
  64. Structure and functional expression of the human macrophage inflammatory protein 1 alpha/RANTES receptor.
    J Exp Med. 1993 May 1;177(5):1421-7 PMID: 7683036
  65. Expression of the transferrin receptor gene during the process of mononuclear phagocyte maturation.
    J Immunol. 1986 Feb 15;136(4):1339-45 PMID: 3003194
  66. Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors. C-C CKR1, a receptor for macrophage inflammatory protein-1 alpha/Rantes, is also a functional receptor for MCP3.
    J Biol Chem. 1995 Sep 22;270(38):22123-8 PMID: 7545673
  67. Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins.
    Science. 1993 Jul 30;261(5121):600-3 PMID: 8342023
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.185.9.1595
Published
1997-05-05
Pages
1595-604
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2196293
Subset
IM
Databases
GENBANK
U83171
External Links
PubMed source DOI: 10.1084/jem.185.9.1595 PMC Full Text View journal details
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