title: Molecular and functional characterization of two novel human C-C chemokines as inhibitors of two distinct classes of myeloid progenitors.
abstract: 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.
authors.affiliation: Department of Cell Biology, Human Genome Sciences, Inc., Rockville, Maryland 20850, USA.
authors.forename: V P
authors.initials: VP
authors.lastname: Patel
authors.forename: B L
authors.initials: BL
authors.lastname: Kreider
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Leung
authors.forename: T
authors.initials: T
authors.lastname: Salcedo
authors.forename: B
authors.initials: B
authors.lastname: Nardelli
authors.forename: V
authors.initials: V
authors.lastname: Pippalla
authors.forename: S
authors.initials: S
authors.lastname: Gentz
authors.forename: R
authors.initials: R
authors.lastname: Thotakura
authors.forename: D
authors.initials: D
authors.lastname: Parmelee
authors.forename: R
authors.initials: R
authors.lastname: Gentz
authors.forename: G
authors.initials: G
authors.lastname: Garotta
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D054423:Chemokine CCL24; D018925:Chemokines / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D019742:Chemokines, CC; D002634:Chemotaxis, Leukocyte; D003001:Cloning, Molecular; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: C105504:CCL23 protein, human; C515484:CCL24 protein, human; C515485:Ccl24 protein, mouse; D054423:Chemokine CCL24; D018925:Chemokines; D019742:Chemokines, CC; D004247:DNA; D002118:Calcium