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

Abstract

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)-1α, 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-1α, 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.

Stromal cells from murine embryonic aorta–gonad–mesonephros region, liver and gut mesentery expand human umbilical cord blood-derived CAFCweek6 in extended long-term cultures

“…31,32 Chemokines, such as the AGM-expressed WECHE, have been reported to inhibit the growth of progenitors. 33,34 These data suggest that the ability of different AGM-derived stromal clones to support human HSCs and progenitors may be explained in part by proportionate differences in expression of stimulatory and inhibitory factors for HSC and progenitor expansion.…”

Biological significance of the expression of HIV-related chemokine coreceptors (CCR5 and CXCR4) and their ligands by human hematopoietic cell lines

“…As an example, MIP-1␣ has been reported to inhibit, [12][13][14][15] stimulate, 16,17 or have no effect on the proliferation of normal human hematopoietic cells. [18][19][20] The other two HIV-related CCR5 binding chemokines (MIP-1␤ and RANTES) did not affect the proliferation of cells. 12,13 SDF-1 -ligand for the CXCR4 receptor has been reported to have no effect on the proliferation of human hematopoietic cells.…”

Eotaxin (CCL11) and Eotaxin-2 (CCL24) Induce Recruitment of Eosinophils, Basophils, Neutrophils, and Macrophages As Well As Features of Early- and Late-Phase Allergic Reactions Following Cutaneous Injection in Human Atopic and Nonatopic Volunteers

“…This chemokine acts on the same receptor as eotaxin and shows the same cellular selectivity, although it is only 39% homologous at the protein level (14). A standardized chemokine nomenclature has recently been introduced, with eotaxin being termed CCL11, and eotaxin-2 being called CCL24.…”