Megaloblastic hematopoiesis in vitro

Interaction of anti-folate receptor antibodies with hematopoietic progenitor cells leads to a proliferative response independent of megaloblastic changes

Asok 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
Pages (from-to)313-325
Number of pages13
JournalJournal of Clinical Investigation
Volume87
Issue number1
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; 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 ; 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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