A NOVEL CHEMOKINE, MACROPHAGE INFLAMMATORY PROTEIN-RELATED PROTEIN-2 INHIBITS COLONY FORMATION OF BONE-MARROW MYELOID PROGENITORS

A new member of the beta-chemokine family, macrophage inflammatory pro tein (MIP)-related protein-2 (MRP-2) was isolated from a murine macrop hage cell line, RAW 264.7. MRP-2 is composed of 122 amino acids of whi ch the first 21 residues constitute a putative signal sequence. The pu tative mature protein is composed of 101 amino acids with a molecular weight of 11,600. MRP-2 is structurally similar to MIP-related protein -1 (MRP-1) (C10) and MIP-1 alpha. MRP-2 shows a 50.8% sequence identit y at the protein level to MRP-1 and a 46.3% identity to MIP-1 alpha. M RP-2 detects approximately 1.3 kilobase mRNA from monocyte and macroph age cell lines but does not detect the mRNA from T and B cells. The MR P-2 gene termed Scya9 was mapped to the central region of mouse chromo some 11 near the Scya1 and Scya2 genes, which are also members of the beta-chemokine superfamily. The Scya gene cluster was located between neurofibromatosis type 1 (Nf1) and myeloperoxidase (Mpo). rMRP-2 signi ficantly suppressed colony formation by murine and human bone marrow g ranulocyte-macrophage (CFU-granulocyte-macrophage), erythroid (burst-f orming unit-E), and multipotential FU-granulocyte-erythroid-macrophage -megakaryocyte) progenitor cells stimulated by combinations of growth factors.