MOLECULAR AND FUNCTIONAL-CHARACTERIZATION OF 2 NOVEL HUMAN C-C CHEMOKINES AS INHIBITORS OF 2 DISTINCT CLASSES OF MYELOID PROGENITORS

Two novel human beta-chemokines, Ck beta-8 or myeloid progenitor inhib itory factor 1 (MPIF-1), and Ck beta-6 or MPIF-2, were discovered as p art of a large scale cDNA sequencing effort. The MPIF-1 and MPIF-2 cDN As were isolated from aortic endothelium and activated monocyte librar ies, respectively. Both of the cDNAs were cloned into a baculovirus ve ctor and expressed in insect cells. The mature recombinant MPIF-1 prot ein consists of 99 amino acids and is most homologous to macrophage in flammatory protein (MIP)-1 alpha, showing 51% identity. It displays ch emotactic activity on resting T lymphocytes and monocytes, a minimal b ut significant activity on neutrophils, and is negative on activated T lymphocytes. MPIF-1 is also a potent suppressor of bone marrow low pr oliferative potential colony-forming cells, a committed progenitor tha t gives rise to granulocyte and monocyte lineages. The mature recombin ant MPIF-2 has 93 amino acid residues and shows 39 and 42% identity wi th monocyte chemoattractant protein (MCP)-3 and MIP-1 alpha, respectiv ely. It displays chemotactic activity on resting T lymphocytes, a mini mal activity on neutrophils, and is negative on monocytes and activate d T lymphocytes. On eosinophils, MPIF-2 produces a transient rise of c ytosolic Ca2+ and uses the receptor for eotaxin and MCP-4. In hematopo ietic assays, MPIF-2 strongly suppressed the colony formation by the h igh proliferative potential colony-forming cell (HPP-CFC), which repre sents a multipotential hematopoietic progenitor.