Comparative analysis of the human macrophage inflammatory protein family of cytokines (chemokines) on proliferation of human myeloid progenitor cells: Interacting effects involving suppression, synergistic suppression, and blocking of suppression

H. E. Broxmeyer, B. Sherry, S. Cooper, L. Lu, R. Maze, M. P. Beckmann, A. Cerami, P. Ralph

Research output: Contribution to journalArticlepeer-review

235 Scopus citations

Abstract

Macrophage inflammatory protein (MIP)-1α, part of a family termed chemokines, has been implicated in suppression of hemopoietic stem and progenitor cell proliferation. The chemokine family has been organized into two subgroups with MIP-1α, MIP-1β, macrophage chemotactic and activating factor (MCAF) and RANTES belonging to one subgroup, and GRO-α, MIP-2α (GRO-β), MIP-2β (GRO-γ), platelet factor 4 (PF4), IL-8, and neutrophil activating peptide (NAP)-2 belonging to the other. These molecules were evaluated for effects on colony formation by human bone marrow multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. None of the chemokines stimulated colony formation in the absence of CSF, or influenced colony formation stimulated by a single growth factor such as granulocyte-macrophage-CSF or erythropoietin. However, MIP-1α, MIP-2α, PF4, IL-8, and MCAF suppressed in dose-response fashion colony formation of immature subsets of myeloid progenitor cells stimulated by GM-CSF plus steel factor. Effects were apparent on low density and CD34+++ HLA-DR+-sorted marrow cells in which up to 88.4% of the cells were composed of progenitor cells, suggesting direct effects on the progenitors themselves. Up to 2500-fold less of each chemokine could be used to demonstrate synergistic suppression when any two of these five chemokines were used together at low concentrations, effects also apparently directly on the progenitors. In contrast, MIP-1β, MIP-2β, GRO-α, NAP-2, and RANTES were not suppressive nor did they synergize with MIP-1α, MIP-2α, PF4, IL-8, or MCAF to suppress. However, a fivefold excess of MIP-1β blocked the suppressive effects of MIP-1α. Similarly, a fivefold excess of either MIP-2β or GRO-α blocked the suppressive effects of IL-8 and PF4. These suppressing, synergizing and blocking effects may be of relevance to blood cell regulation.

Original languageEnglish (US)
Pages (from-to)3448-3458
Number of pages11
JournalJournal of Immunology
Volume150
Issue number8 I
StatePublished - 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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