title: Macrophage inflammatory protein 1alpha enhances in a different manner adhesion of hematopoietic progenitor cells from bone marrow, cord blood, and mobilized peripheral blood.
abstract: Regulatory mechanisms governing adhesion of hematopoietic progenitor cells to the stromal nische are poorly understood. Growth factors such as stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor, and thrombopoietin were reported to upregulate the adhesion of hematopoietic progenitors to immobilized fibronectin through activation of integrin alpha4beta1 and alpha5beta1. Macrophage inflammatory protein (MIP)-1alpha is a C-C chemokine that suppresses colony formation by stem/progenitor cells in vitro. We asked if MIP-1alpha would modulate the adhesive phenotype of colony-forming cells (CFCs) obtained from healthy donor bone marrow (BM), cord blood (CB), and mobilized peripheral blood (mPB) CD34+ cells, in comparison with SCF, using immobilized fibronectin. SCF significantly increased the level of adhesion of CFCs from BM, CB, and mPB. On the other hand, MIP-1alpha significantly increased the level of adhesion of CFCs from BM and CB, but less so from mPB. The effects of MIP-1alpha were inhibited by blocking antibodies to integrin alpha4, alpha5, or beta1, and polymerization plus rearrangement of F-actin were observed in affected cells by labeling with rhodamine-conjugated phalloidine. These data indicate that the effect of MIP-1alpha on the adhesive phenotype of CFCs is mediated by modulation of the organization of integrin. The amount of MIP-1alpha receptor on mPB was less than for BM or CB, which may explain the distinct characteristics in the adhesive response induced by MIP-1alpha. We suggest that hematopoietic progenitor cells from different sources may be heterogeneous with respect to maturation, integrin affinity, MIP-1alpha receptor expression, and regulation of MIP-1alpha signaling. Our data indicate that MIP-1alpha may affect migration, homing, and mobilization of hematopoietic progenitors by modulating the adhesive phenotype of these cells.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Oita, Japan. ysss@tsurumi.beppu.kyushu-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Suehiro
authors.forename: K
authors.initials: K
authors.lastname: Muta
authors.forename: T
authors.initials: T
authors.lastname: Umemura
authors.forename: Y
authors.initials: Y
authors.lastname: Abe
authors.forename: J
authors.initials: J
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Nawata
mesh_terms: D000199:Actins / Q000737:chemistry; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34 / Q000097:blood; D001704:Biopolymers; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003114:Colony-Forming Units Assay; D003599:Cytoskeleton / Q000187:drug effects; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects*; D005353:Fibronectins / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D014019:Tissue Donors
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D001704:Biopolymers; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D005353:Fibronectins; D019402:Macrophage Inflammatory Proteins