Megaloblastic hematopoiesis in vitro: Interaction of anti-folate receptor antibodies with hematopoietic progenitor cells leads to a proliferative response independent of megaloblastic changes

Asok C. Antony, Robert A. Briddell, John E. Brandt, John E. Straneva, Rama S. Verma, Michael E. Miller, Lorrie A. Kalasinski, Ronald Hoffman

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We tested the hypothesis that anti-placental folate receptor (PFR) antiserum-mediated effects on hematopoietic progenitor cells in vitro of increased cell proliferation and megaloblastic morphology were independent responses. We determined that (a) purified IgG from anti-PFR antiserum reacted with purified apo- and holo-PFR and specifically immunoprecipitated a single (44-kD) iodinated moiety on cell surfaces of low density mononuclear cells (LDMNC); (b) when retained in culture during in vitro hematopoiesis, anti-PFR IgG (in contrast to PFR-neutralized anti-PFR IgG and nonimmune IgG) consistently led to increased cloning efficiency of colony forming unit-erythroid (CFU-E), burst forming unit-E (BFU-E), CFU-granulocyte macrophage (CFU-GM), and CFU-GEM megakaryocyte (CFU-GEMM), and objectively defined megaloblastic changes in orthochromatic normoblasts from CFU-E- and BFU-E-derived colonies; (c) when anti-PFR antiserum was removed after initial (< 1 h) incubation with LDMNC, a cell proliferation response was induced, but megaloblastic changes were not evident. (d) Conversely, delay at 4°C for 24 h before long-term plating with antiserum resulted in megaloblastosis without increased cell proliferation; (e) however, 500-fold molar excess extracellular folate concentrations completely abrogated the expected anti-PFR antiserum-induced megaloblastic changes, without altering cell proliferative responses. Thus, although cell proliferative and megaloblastic changes are induced after short-term and prolonged interaction of antibody with folate receptors on hematopoietic progenitors, respectively, they are independent effects.

Original languageEnglish (US)
Pages (from-to)313-325
Number of pages13
JournalJournal of Clinical Investigation
Volume87
Issue number1
DOIs
StatePublished - Jan 1991

Fingerprint

Folate Receptor 2
Hematopoiesis
Hematopoietic Stem Cells
Folic Acid
Antibodies
Immune Sera
Erythroid Precursor Cells
Immunoglobulin G
Cell Proliferation
Stem Cells
Cell Count
Erythroblasts
Megakaryocytes
In Vitro Techniques
Granulocytes
Organism Cloning
Macrophages

Keywords

  • Bone marrow
  • Folate binding
  • Hyperplasia
  • Megaloblastosis
  • Morphology
  • Transport

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Megaloblastic hematopoiesis in vitro : Interaction of anti-folate receptor antibodies with hematopoietic progenitor cells leads to a proliferative response independent of megaloblastic changes. / Antony, Asok C.; Briddell, Robert A.; Brandt, John E.; Straneva, John E.; Verma, Rama S.; Miller, Michael E.; Kalasinski, Lorrie A.; Hoffman, Ronald.

In: Journal of Clinical Investigation, Vol. 87, No. 1, 01.1991, p. 313-325.

Research output: Contribution to journalArticle

Antony, Asok C. ; Briddell, Robert A. ; Brandt, John E. ; Straneva, John E. ; Verma, Rama S. ; Miller, Michael E. ; Kalasinski, Lorrie A. ; Hoffman, Ronald. / Megaloblastic hematopoiesis in vitro : Interaction of anti-folate receptor antibodies with hematopoietic progenitor cells leads to a proliferative response independent of megaloblastic changes. In: Journal of Clinical Investigation. 1991 ; Vol. 87, No. 1. pp. 313-325.
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AB - We tested the hypothesis that anti-placental folate receptor (PFR) antiserum-mediated effects on hematopoietic progenitor cells in vitro of increased cell proliferation and megaloblastic morphology were independent responses. We determined that (a) purified IgG from anti-PFR antiserum reacted with purified apo- and holo-PFR and specifically immunoprecipitated a single (44-kD) iodinated moiety on cell surfaces of low density mononuclear cells (LDMNC); (b) when retained in culture during in vitro hematopoiesis, anti-PFR IgG (in contrast to PFR-neutralized anti-PFR IgG and nonimmune IgG) consistently led to increased cloning efficiency of colony forming unit-erythroid (CFU-E), burst forming unit-E (BFU-E), CFU-granulocyte macrophage (CFU-GM), and CFU-GEM megakaryocyte (CFU-GEMM), and objectively defined megaloblastic changes in orthochromatic normoblasts from CFU-E- and BFU-E-derived colonies; (c) when anti-PFR antiserum was removed after initial (< 1 h) incubation with LDMNC, a cell proliferation response was induced, but megaloblastic changes were not evident. (d) Conversely, delay at 4°C for 24 h before long-term plating with antiserum resulted in megaloblastosis without increased cell proliferation; (e) however, 500-fold molar excess extracellular folate concentrations completely abrogated the expected anti-PFR antiserum-induced megaloblastic changes, without altering cell proliferative responses. Thus, although cell proliferative and megaloblastic changes are induced after short-term and prolonged interaction of antibody with folate receptors on hematopoietic progenitors, respectively, they are independent effects.

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