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Ronald Godiska^*, David Chantry^*, Carol J. Raport^*, Silvano Sozzani, Paola Allavena, Dina Leviten^*, Alberto Mantovani, and Patrick W. Gray^*

From the ^* Icos Corporation, Bothell, Washington 98021; and Istituto di Ricerche Farmacologiche "Mario Negri", I-20157 Milan, Italy

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 macrophagederived 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.

P. Allavena, S. Sozzani, and A. Mantovani were supported by Project AIDS, Istituto Superiore Sanitá, and Associazione Italiana per la Recerca sul Cancro.

¹Abbreviations used in this paper: CHO, Chinese hamster ovary; GAPDH, glyceraldehyde phosphate dehydrogenase; I-HUVEC, immortalized human umbilical vein endothelial cells; LDL, low density lipoprotein; MCP, monocyte chemotactic proteins; MDC, macrophage-derived chemokine; MIP, macrophage inflammatory protein; TARC, thymus and activation regulated chemokine.

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• Proost, P., Struyf, S., Schols, D., Opdenakker, G., Sozzani, S., Allavena, P., Mantovani, A., Augustyns, K., Bal, G., Haemers, A., Lambeir, A.-M., Scharpe, S., Van Damme, J., De Meester, I. (1999). Truncation of Macrophage-derived Chemokine by CD26/ Dipeptidyl-Peptidase IV beyond Its Predicted Cleavage Site Affects Chemotactic Activity and CC Chemokine Receptor 4 Interaction. J. Biol. Chem. 274: 3988-3993 [Abstract] [Full Text]  
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• Meucci, O., Fatatis, A., Simen, A. A., Bushell, T. J., Gray, P. W., Miller, R. J. (1998). Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. Proc. Natl. Acad. Sci. USA 95: 14500-14505 [Abstract] [Full Text]  
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• Bonecchi, R., Sozzani, S., Stine, J. T., Luini, W., D'Amico, G., Allavena, P., Chantry, D., Mantovani, A. (1998). Divergent Effects of Interleukin-4 and Interferon-gamma on Macrophage-Derived Chemokine Production: An Amplification Circuit of Polarized T Helper 2 Responses. Blood 92: 2668-2671 [Abstract] [Full Text]  
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• Schaniel, C., Pardali, E., Sallusto, F., Speletas, M., Ruedl, C., Shimizu, T., Seidl, T., Andersson, J., Melchers, F., Rolink, A. G., Sideras, P. (1998). Activated Murine B Lymphocytes and Dendritic Cells Produce a Novel CC Chemokine which Acts Selectively on Activated T Cells. JEM 188: 451-463 [Abstract] [Full Text]  
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• Fioretti, F., Fradelizi, D., Stoppacciaro, A., Ramponi, S., Ruco, L., Minty, A., Sozzani, S., Garlanda, C., Vecchi, A., Mantovani, A. (1998). Reduced Tumorigenicity and Augmented Leukocyte Infiltration After Monocyte Chemotactic Protein-3 (MCP-3) Gene Transfer: Perivascular Accumulation of Dendritic Cells in Peritumoral Tissue and Neutrophil Recruitment Within the Tumor. J. Immunol. 161: 342-346 [Abstract] [Full Text]  
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• Yoshida, R., Nagira, M., Kitaura, M., Imagawa, N., Imai, T., Yoshie, O. (1998). Secondary Lymphoid-tissue Chemokine Is a Functional Ligand for the CC Chemokine Receptor CCR7. J. Biol. Chem. 273: 7118-7122 [Abstract] [Full Text]  
• Kodelja, V., Muller, C., Politz, O., Hakij, N., Orfanos, C. E., Goerdt, S. (1998). Alternative Macrophage Activation-Associated CC-Chemokine-1, a Novel Structural Homologue of Macrophage Inflammatory Protein-1{alpha} with a Th2-Associated Expression Pattern. J. Immunol. 160: 1411-1418 [Abstract] [Full Text]  
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• Bonecchi, R., Bianchi, G., Bordignon, P. P., D'Ambrosio, D., Lang, R., Borsatti, A., Sozzani, S., Allavena, P., Gray, P. A., Mantovani, A., Sinigaglia, F. (1998). Differential Expression of Chemokine Receptors and Chemotactic Responsiveness of Type 1 T Helper Cells (Th1s) and Th2s. JEM 187: 129-134 [Abstract] [Full Text]  
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• Pal, R., Garzino-Demo, A., Markham, P. D., Burns, J., Brown, M., Gallo, R. C., DeVico, A. L. (1997). Inhibition of HIV-1 Infection by the -Chemokine MDC. Science 278: 695-698 [Abstract] [Full Text]  
• Khabar, K. S.A., Al-Zoghaibi, F., Al-Ahdal, M. N., Murayama, T., Dhalla, M., Mukaida, N., Taha, M., Al-Sedairy, S. T., Siddiqui, Y., Kessie, G., Matsushima, K. (1997). The {alpha} Chemokine, Interleukin 8, Inhibits the Antiviral Action of Interferon {alpha}. JEM 186: 1077-1085 [Abstract] [Full Text]  
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