J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/04/1163/10 $2.00
Volume 185, Number 7, April 7, 1997 1163-1172

Molecular and Functional Characterization of  Two Novel Human C-C Chemokines as Inhibitors of  Two Distinct Classes of Myeloid Progenitors

By Vikram P. Patel,^* Brent L. Kreider,^* Yuling Li,^§ Haodong Li, Kam Leung,^* Theodora Salcedo,^* Bernardetta Nardelli,^* Vani Pippalla,^* Solange Gentz,^§ Rao Thotakura,^§ David Parmelee,^§ Reiner Gentz,^§ and Gianni Garotta^*

From the ^* Department of Cell Biology,  Department of Protein Therapeutics, and ^§ Department of Protein Expression and Purification, Human Genome Sciences, Inc., Rockville, Maryland 20850

Two novel human -chemokines, Ck-8 or myeloid progenitor inhibitory factor 1 (MPIF-1), and Ck-6 or MPIF-2, were discovered as part of a large scale cDNA sequencing effort. The MPIF-1 and MPIF-2 cDNAs were isolated from aortic endothelium and activated monocyte libraries, respectively. Both of the cDNAs were cloned into a baculovirus vector and expressed in insect cells. The mature recombinant MPIF-1 protein consists of 99 amino acids and is most homologous to macrophage inflammatory protein (MIP)-1, showing 51% identity. It displays chemotactic activity on resting T lymphocytes and monocytes, a minimal but significant activity on neutrophils, and is negative on activated T lymphocytes. MPIF-1 is also a potent suppressor of bone marrow low proliferative potential colony-forming cells, a committed progenitor that gives rise to granulocyte and monocyte lineages. The mature recombinant MPIF-2 has 93 amino acid residues and shows 39 and 42% identity with monocyte chemoattractant protein (MCP)-3 and MIP-1, respectively. It displays chemotactic activity on resting T lymphocytes, a minimal activity on neutrophils, and is negative on monocytes and activated T lymphocytes. On eosinophils, MPIF-2 produces a transient rise of cytosolic Ca²⁺ and uses the receptor for eotaxin and MCP-4. In hematopoietic assays, MPIF-2 strongly suppressed the colony formation by the high proliferative potential colony-forming cell (HPP-CFC), which represents a multipotential hematopoietic progenitor.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Cicinnati, V. R., Kang, J., Sotiropoulos, G. C., Hilgard, P., Frilling, A., Broelsch, C. E., Gerken, G., Beckebaum, S. (2008). Altered chemotactic response of myeloid and plasmacytoid dendritic cells from patients with chronic hepatitis C: role of alpha interferon. J. Gen. Virol. 89: 1243-1253 [Abstract] [Full Text]  
• Miao, Z., Premack, B. A., Wei, Z., Wang, Y., Gerard, C., Showell, H., Howard, M., Schall, T. J., Berahovich, R. (2007). Proinflammatory Proteases Liberate a Discrete High-Affinity Functional FPRL1 (CCR12) Ligand from CCL23. J. Immunol. 178: 7395-7404 [Abstract] [Full Text]  
• Novak, H., Muller, A., Harrer, N., Gunther, C., Carballido, J. M., Woisetschlager, M. (2007). CCL23 Expression Is Induced by IL-4 in a STAT6-Dependent Fashion. J. Immunol. 178: 4335-4341 [Abstract] [Full Text]  
• Hurst, J. R., Donaldson, G. C., Perera, W. R., Wilkinson, T. M. A., Bilello, J. A., Hagan, G. W., Vessey, R. S., Wedzicha, J. A. (2006). Use of Plasma Biomarkers at Exacerbation of Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 174: 867-874 [Abstract] [Full Text]  
• Steinbach, D., Schramm, A., Eggert, A., Onda, M., Dawczynski, K., Rump, A., Pastan, I., Wittig, S., Pfaffendorf, N., Voigt, A., Zintl, F., Gruhn, B. (2006). Identification of a Set of Seven Genes for the Monitoring of Minimal Residual Disease in Pediatric Acute Myeloid Leukemia. Clin. Cancer Res. 12: 2434-2441 [Abstract] [Full Text]  
• Min, J.-W., Jang, A.-S., Park, S.-M., Lee, S.-H., Lee, J.-H., Park, S.-W., Park, C.-S. (2005). Comparison of Plasma Eotaxin Family Level in Aspirin-Induced and Aspirin-Tolerant Asthma Patients. Chest 128: 3127-3132 [Abstract] [Full Text]  
• Pope, S. M., Zimmermann, N., Stringer, K. F., Karow, M. L., Rothenberg, M. E. (2005). The Eotaxin Chemokines and CCR3 Are Fundamental Regulators of Allergen-Induced Pulmonary Eosinophilia. J. Immunol. 175: 5341-5350 [Abstract] [Full Text]  
• Pope, S. M., Fulkerson, P. C., Blanchard, C., Akei, H. S., Nikolaidis, N. M., Zimmermann, N., Molkentin, J. D., Rothenberg, M. E. (2005). Identification of a Cooperative Mechanism Involving Interleukin-13 and Eotaxin-2 in Experimental Allergic Lung Inflammation. J. Biol. Chem. 280: 13952-13961 [Abstract] [Full Text]  
• Umland, O., Heine, H., Miehe, M., Marienfeld, K., Staubach, K. H., Ulmer, A. J. (2004). Induction of various immune modulatory molecules in CD34+ hematopoietic cells. J. Leukoc. Biol. 75: 671-679 [Abstract] [Full Text]  
• Shin, H. D., Kim, L. H., Park, B. L., Jung, J. H., Kim, J. Y., Chung, I.-Y., Kim, J. S., Lee, J. H., Chung, S. H., Kim, Y. H., Park, H.-S., Choi, J. H., Lee, Y. M., Park, S. W., Choi, B. W., Hong, S.-J., Park, C.-S. (2003). Association of Eotaxin gene family with asthma and serum total IgE. Hum Mol Genet 12: 1279-1285 [Abstract] [Full Text]  
• Menzies-Gow, A., Ying, S., Sabroe, I., Stubbs, V. L., Soler, D., Williams, T. J., Kay, A. B. (2002). Eotaxin (CCL11) and Eotaxin-2 (CCL24) Induce Recruitment of Eosinophils, Basophils, Neutrophils, and Macrophages As Well As Features of Early- and Late-Phase Allergic Reactions Following Cutaneous Injection in Human Atopic and Nonatopic Volunteers. J. Immunol. 169: 2712-2718 [Abstract] [Full Text]  
• Watanabe, K., Jose, P. J., Rankin, S. M. (2002). Eotaxin-2 Generation Is Differentially Regulated by Lipopolysaccharide and IL-4 in Monocytes and Macrophages. J. Immunol. 168: 1911-1918 [Abstract] [Full Text]  
• Ottersbach, K., Cook, D. N., Kuziel, W. A., Humbles, A., Lu, B., Gerard, C., Proudfoot, A. E. I., Graham, G. J. (2001). Macrophage inflammatory protein-1alpha uses a novel receptor for primitive hemopoietic cell inhibition. Blood 98: 3476-3478 [Abstract] [Full Text]  
• Forssmann, U., Magert, H.-J., Adermann, K., Escher, S. E., Forssmann, W.-G. (2001). Hemofiltrate CC chemokines with unique biochemical properties: HCC-1/CCL14a and HCC-2/CCL15. J. Leukoc. Biol. 70: 357-366 [Abstract] [Full Text]  
• Nomiyama, H., Hieshima, K., Nakayama, T., Sakaguchi, T., Fujisawa, R., Tanase, S., Nishiura, H., Matsuno, K., Takamori, H., Tabira, Y., Yamamoto, T., Miura, R., Yoshie, O. (2001). Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for CCR1, CCR2 and CCR5, and constitutively expressed by hepatocytes. Int Immunol 13: 1021-1029 [Abstract] [Full Text]  
• Zimmermann, N., Hogan, S. P., Mishra, A., Brandt, E. B., Bodette, T. R., Pope, S. M., Finkelman, F. D., Rothenberg, M. E. (2000). Murine Eotaxin-2: A Constitutive Eosinophil Chemokine Induced by Allergen Challenge and IL-4 Overexpression. J. Immunol. 165: 5839-5846 [Abstract] [Full Text]  
• Sleeman, M. A., Fraser, J. K., Murison, J. G., Kelly, S. L., Prestidge, R. L., Palmer, D. J., Watson, J. D., Kumble, K. D. (2000). B cell- and monocyte-activating chemokine (BMAC), a novel non-ELR {alpha}-chemokine. Int Immunol 12: 677-689 [Abstract] [Full Text]  
• Bowman, E. P., Campbell, J. J., Soler, D., Dong, Z., Manlongat, N., Picarella, D., Hardy, R. R., Butcher, E. C. (2000). Developmental Switches in Chemokine Response Profiles during B Cell Differentiation and Maturation. JEM 191: 1303-1318 [Abstract] [Full Text]  
• Majka, M., Ratajczak, J., Lee, B., Honczarenko, M., Douglas, R., Kowalska, M. A., Silberstein, L., Gewirtz, A. M., Ratajczak, M. Z. (2000). The Role of HIV-Related Chemokine Receptors and Chemokines in Human Erythropoiesis in Vitro. Stem Cells 18: 128-138 [Abstract] [Full Text]  
• Kitaura, M., Suzuki, N., Imai, T., Takagi, S., Suzuki, R., Nakajima, T., Hirai, K., Nomiyama, H., Yoshie, O. (1999). Molecular Cloning of a Novel Human CC Chemokine (Eotaxin-3) That Is a Functional Ligand of CC Chemokine Receptor 3. J. Biol. Chem. 274: 27975-27980 [Abstract] [Full Text]  
• Jahnsen, F. L., Haye, R., Gran, E., Brandtzaeg, P., Johansen, F.-E. (1999). Glucocorticosteroids Inhibit mRNA Expression for Eotaxin, Eotaxin-2, and Monocyte-Chemotactic Protein-4 in Human Airway Inflammation with Eosinophilia. J. Immunol. 163: 1545-1551 [Abstract] [Full Text]  
• Struyf, S., Proost, P., Schols, D., De Clercq, E., Opdenakker, G., Lenaerts, J.-P., Detheux, M., Parmentier, M., De Meester, I., Scharpe, S., Van Damme, J. (1999). CD26/Dipeptidyl-Peptidase IV Down-Regulates the Eosinophil Chemotactic Potency, But Not the Anti-HIV Activity of Human Eotaxin by Affecting Its Interaction with CC Chemokine Receptor 3. J. Immunol. 162: 4903-4909 [Abstract] [Full Text]  
• Zhang, S., Youn, B.-S., Gao, J.-L., Murphy, P. M., Kwon, B. S. (1999). Differential Effects of Leukotactin-1 and Macrophage Inflammatory Protein-1{alpha} on Neutrophils Mediated by CCR1. J. Immunol. 162: 4938-4942 [Abstract] [Full Text]  
• Teruya-Feldstein, J., Jaffe, E. S., Burd, P. R., Kingma, D. W., Setsuda, J. E., Tosato, G. (1999). Differential Chemokine Expression in Tissues Involved by Hodgkin's Disease: Direct Correlation of Eotaxin Expression and Tissue Eosinophilia. Blood 93: 2463-2470 [Abstract] [Full Text]  
• Nardelli, B., Tiffany, H. L., Bong, G. W., Yourey, P. A., Morahan, D. K., Li, Y., Murphy, P. M., Alderson, R. F. (1999). Characterization of the Signal Transduction Pathway Activated in Human Monocytes and Dendritic Cells by MPIF-1, a Specific Ligand for CC Chemokine Receptor 1. J. Immunol. 162: 435-444 [Abstract] [Full Text]  
• Macphee, C. H., Appelbaum, E. R., Johanson, K., Moores, K. E., Imburgia, C. S., Fornwald, J., Berkhout, T., Brawner, M., Groot, P. H. E., O'Donnell, K., O'Shannessy, D., Scott, G., White, J. R. (1998). Identification of a Truncated Form of the CC Chemokine CK{beta}-8 Demonstrating Greatly Enhanced Biological Activity. J. Immunol. 161: 6273-6279 [Abstract] [Full Text]  
• Cashman, J.D., Eaves, C.J., Sarris, A.H., Eaves, A.C. (1998). MCP-1, not MIP-1alpha , Is the Endogenous Chemokine That Cooperates With TGF-beta to Inhibit the Cycling of Primitive Normal but not Leukemic (CML) Progenitors in Long-Term Human Marrow Cultures. Blood 92: 2338-2344 [Abstract] [Full Text]  
• Kim, C. H., Pelus, L. M., White, J. R., Broxmeyer, H. E. (1998). Macrophage-Inflammatory Protein-3{beta}/EBI1-Ligand Chemokine/CK{beta}-11, a CC Chemokine, Is a Chemoattractant with a Specificity for Macrophage Progenitors Among Myeloid Progenitor Cells. J. Immunol. 161: 2580-2585 [Abstract] [Full Text]  
• Youn, B.-S., Zhang, S. M., Broxmeyer, H. E., Cooper, S., Antol, K., Fraser, M. Jr, Kwon, B. S. (1998). Characterization of CKbeta 8 and CKbeta 8-1: Two Alternatively Spliced Forms of Human beta -Chemokine, Chemoattractants for Neutrophils, Monocytes, and Lymphocytes, and Potent Agonists at CC Chemokine Receptor 1 . Blood 91: 3118-3126 [Abstract] [Full Text]  
• 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]  
• Forssmann, U., Uguccioni, M., Loetscher, P., Dahinden, C. A., Langen, H., Thelen, M., Baggiolini, M. (1997). Eotaxin-2, a Novel CC Chemokine that Is Selective for the Chemokine Receptor CCR3, and Acts Like Eotaxin on Human Eosinophil and Basophil Leukocytes. JEM 185: 2171-2176 [Abstract] [Full Text]  
• Rajarathnam, K., Li, Y., Rohrer, T., Gentz, R. (2001). Solution Structure and Dynamics of Myeloid Progenitor Inhibitory Factor-1 (MPIF-1), A Novel Monomeric CC Chemokine. J. Biol. Chem. 276: 4909-4916 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS