Regulatory action of prolactin on the in vitro growth of CD34+ve human hemopoietic progenitor cells

Abstract

The pituitary hormone prolactin (Prl) is known to act as a local regulator of immune cell function, and Prl-binding receptors (Prl-R) have been described to share distinctive features with the members of the newly described cytokine/hemopoietin receptor superfamily. Here we show that the hormone can functionally interact with lineage-specific hemopoietic factors. When highly purified progenitor cells (CD34+ve) were seeded in semisolid methylcellulose cultures in the presence of interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), and erythropoietin (Epo), a selective enhancing effect of Prl on the formation of colony forming unit-granulocyte (CFU-G) and burst forming unit-erythroid (BFU-E) colonies was observed. The effect of the hormone was plotted as a bell shaped curve, with the optimal response at the supraphysiological concentration of 50 ng/ml. Limiting dilution analysis showed that Prl acted directly on hemopoietic progenitors. This was confirmed by the observation on the CD34+ve cells of Prl-binding sites reacting with the specific monoclonal antibodies (mAbs), U5 and PrR-7A. Immunoprecipitation of the metabolically labeled CD34+ve cells with the PrR-7A mAb revealed a structure of 43 kD under reducing conditions. Analysis of the early events associated with the Prl/Prl-R interaction showed an increased number of cells engaged in DNA and hemoglobin synthesis. Enhanced erythroid differentiation of CD34+ve cells in the presence of Prl was secondary to upmodulation of receptors for the lineage-specific factor Epo. Together these data demonstrate the existence of a functional interplay between Prl and hemopoietic factors.

Human Prolactin Promotes Human Secondary Immunoglobulin Response in Human/SCID Mouse Chimeras

“…Treatment with PRL in serum-free medium independently or synergistically with IL-2 enhanced the natural cytotoxicity of human NK and lymphokine-activated killer cells to tumor targets (7). PRL was reported to improve stem cell differentiation in a semisolid colony assay system (5). We also observed that PRL administration increased the antigen-specific proliferation of lymph node T cells in both normal and dwarf mice (20).…”

Senior Author Correspondence Information

“…PRL and GH play a role in stimulating the hematopoietic system (Bellone et al, 1995;Richards and Murphy, 2000). PRL enhances granulocyte/macrophagecolony stimulating factor (GM-CSF)-mediated maturation of CD34ϩ human hematopoietic progenitor cells into erythroid precursors in culture (Bellone et al, 1995).…”

“…PRL enhances granulocyte/macrophagecolony stimulating factor (GM-CSF)-mediated maturation of CD34ϩ human hematopoietic progenitor cells into erythroid precursors in culture (Bellone et al, 1995). Pharmacologic levels of PRL increase the hematopoietic progenitors of the myeloid (colony-forming unit-granulocyte macrophage, or CFU-GM) and erythroid (blast-forming unit-erythocyte, or BFU-E) lineages in the bone marrow and spleen, during myelosuppression following treatment for HIV infection or bone marrow transplantation (Richards and Murphy, 2000).…”

“…Pharmacologic levels of PRL increase the hematopoietic progenitors of the myeloid (colony-forming unit-granulocyte macrophage, or CFU-GM) and erythroid (blast-forming unit-erythocyte, or BFU-E) lineages in the bone marrow and spleen, during myelosuppression following treatment for HIV infection or bone marrow transplantation (Richards and Murphy, 2000). PRL also increases the number of progenitors of other immune cell lineages, including T cells, B cells, and NK cells (Bellone et al, 1995). In various diseases, PRL antagonizes the immunosuppressive effects of transforming growth factor-beta (TGF-␤) (Richards et al, 1998), tumor necrosis factor alpha (TNF␣) (Luo and Yu-Lee, 2000), or corticosterone (LaVoie and Witorsch, 1995;) and thus may enhance recovery of the hematopoietic system.…”

Individual and combined effect of granulocyte–macrophage colony‐stimulating factor and prolactin on maturation of dendritic cells from blood monocytes under serum‐free conditions

“…They thus become active T-cell stimulators. Because PRL has been shown by our group to interact with GM-CSF, 16,17 we have here addressed its possible involvement, alone or in combination with GM-CSF, in the process of DC maturation and antigen presentation. Sigma-Aldrich s.r.l (Gallarate, Milan, Italy).…”