Molecular and functional characterization of two novel human C-C chemokines as inhibitors of two distinct classes of myeloid progenitors.
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.
Patel
V P
VP
Department of Cell Biology, Human Genome Sciences, Inc., Rockville, Maryland 20850, USA.
Kreider
B L
BL
Li
Y
Y
Li
H
H
Leung
K
K
Salcedo
T
T
Nardelli
B
B
Pippalla
V
V
Gentz
S
S
Thotakura
R
R
Parmelee
D
D
Gentz
R
R
Garotta
G
G
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
C105504:CCL23 protein, human; C515484:CCL24 protein, human; C515485:Ccl24 protein, mouse; D054423:Chemokine CCL24; D018925:Chemokines; D019742:Chemokines, CC; D004247:DNA; D002118:Calcium