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

Hal Broxmeyer, Barbara Sherry, Scott Cooper, Li Lu, Rodney Maze, M. Patricia Beckmann, Anthony Cerami, Peter Ralph

Research output: Contribution to journalArticle

227 Citations (Scopus)

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
Pages (from-to)3448-3458
Number of pages11
JournalJournal of Immunology
Volume150
Issue number8 PART 1
StatePublished - 1993

Fingerprint

Myeloid Progenitor Cells
Macrophage Inflammatory Proteins
Chemokine CXCL2
Chemokines
Cytokines
Platelet Factor 4
Macrophage-Activating Factors
Interleukin-8
Chemotactic Factors
Stem Cells
Chemokine CCL5
Granulocytes
Bone Marrow
Macrophages
Granulocyte-Macrophage Progenitor Cells
Erythroid Precursor Cells
Stem Cell Factor
HLA-DR Antigens
Granulocyte-Macrophage Colony-Stimulating Factor
Erythropoietin

ASJC Scopus subject areas

  • Immunology

Cite this

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. / Broxmeyer, Hal; Sherry, Barbara; Cooper, Scott; Lu, Li; Maze, Rodney; Beckmann, M. Patricia; Cerami, Anthony; Ralph, Peter.

In: Journal of Immunology, Vol. 150, No. 8 PART 1, 1993, p. 3448-3458.

Research output: Contribution to journalArticle

@article{0fe2d1123a0f4473866fd00bfac62c84,
title = "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",
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.",
author = "Hal Broxmeyer and Barbara Sherry and Scott Cooper and Li Lu and Rodney Maze and Beckmann, {M. Patricia} and Anthony Cerami and Peter Ralph",
year = "1993",
language = "English",
volume = "150",
pages = "3448--3458",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "8 PART 1",

}

TY - JOUR

T1 - Comparative analysis of the human macrophage inflammatory protein family of cytokines (chemokines) on proliferation of human myeloid progenitor cells

T2 - Interacting effects involving suppression, synergistic suppression, and blocking of suppression

AU - Broxmeyer, Hal

AU - Sherry, Barbara

AU - Cooper, Scott

AU - Lu, Li

AU - Maze, Rodney

AU - Beckmann, M. Patricia

AU - Cerami, Anthony

AU - Ralph, Peter

PY - 1993

Y1 - 1993

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0027300330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027300330&partnerID=8YFLogxK

M3 - Article

C2 - 7682242

AN - SCOPUS:0027300330

VL - 150

SP - 3448

EP - 3458

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 8 PART 1

ER -