The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/4/1163/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 7, April 7, 1997 1163-1172

Article

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

Vikram P. Patel*, Brent L. Kreider*, Yuling Li§, Haodong Li{ddagger}, 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, {ddagger} Department of Protein Therapeutics, and § Department of Protein Expression and Purification, Human Genome Sciences, Inc., Rockville, Maryland 20850

Two novel human β-chemokines, Ckβ-8 or myeloid progenitor inhibitory factor 1 (MPIF-1), and Ckβ-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{alpha}, 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{alpha}, 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.

Address correspondence to Dr. Vikram Patel, Cell Biology Department, Human Genome Sciences, Inc., 9410 Key West Ave., Rockville, MD 20850.

1Abbreviations used in this paper: CFC, colony-forming cells; Epo, erythropoietin; EST, expressed sequence tag; FBS, fetal bovine serum; GM, granulocyte and monocyte; h, human; HPP, high proliferative potential; LPP, low proliferative potential; m, mouse; MCP, monocyte chemoattractant protein; MIP, macrophage inflammatory protein; MPIF, myeloid progenitor inhibitory factors; PAF, platelet-activating factor; SCF, stem cell factor.


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