Megaloblastic hematopoiesis in vitro. Interaction of anti-folate receptor antibodies with hematopoietic progenitor cells leads to a proliferative response independent of megaloblastic changes.
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 (less than 1 h) incubation with LDMNC, a cell proliferation response was induced, but megaloblastic changes were not evident. (d) Conversely, delay at 4 degrees 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.
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5121.
A C
AC
Antony
R A
RA
Briddell
J E
JE
Brandt
J E
JE
Straneva
R S
RS
Verma
M E
ME
Miller
L A
LA
Kalasinski
R
R
Hoffman
D000818:Animals; D002352:Carrier Proteins / Q000276:immunology / Q000502:physiology*; D002455:Cell Division; D004247:DNA / Q000032:analysis; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008264:Macrophages / Q000502:physiology; D008534:Megaloblasts / Q000502:physiology*; D012313:RNA / Q000032:analysis; D011817:Rabbits; D011956:Receptors, Cell Surface; D013601:T-Lymphocytes / Q000502:physiology
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D007106:Immune Sera; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; D012313:RNA; D004247:DNA; D005492:Folic Acid