Molecular and functional characterization of two novel human C-C chemokines as inhibitors of two distinct classes of myeloid progenitors

• Published in: The Journal of experimental medicine Vol. 185; no. 7; pp. 1163 - 1172
• Main Authors: Patel, V P, Kreider, B L, Li, Y, Li, H, Leung, K, Salcedo, T, Nardelli, B, Pippalla, V, Gentz, S, Thotakura, R, Parmelee, D, Gentz, R, Garotta, G
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 07.04.1997
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Calcium - metabolism; Chemokine CCL24; Chemokines - genetics; Chemokines - isolation & purification; Chemokines - pharmacology; Chemokines, CC; Chemotaxis, Leukocyte; Cloning, Molecular; Cytosol - metabolism; DNA - genetics; Dose-Response Relationship, Drug; Hematopoietic Stem Cells - drug effects; Humans; Mice; Molecular Sequence Data; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Tissue Distribution
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.185.7.1163

Two novel human beta-chemokines, Ck beta-8 or myeloid progenitor inhibitory factor 1 (MPIF-1), and Ck beta-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)-1alpha, 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-1alpha, 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.