Human serum megakaryocyte colony-stimulating activity appears to be distinct from interleukin-3, granulocyte-macrophage colony-stimulating factor, and lymphocyte-conditioned medium.
Sera from patients with bone marrow megakaryocyte aplasia are a rich source of megakaryocyte colony-stimulating activity (Meg-CSA). Other biologic materials exhibiting Meg-CSA include phytohemagglutinin-stimulated human lymphocyte-conditioned medium (PHA-LCM), recombinant interleukin-3 (IL-3), and recombinant granulocyte macrophage colony-stimulating factor (GM-CSF). Neutralizing antisera to both recombinant IL-3 and GM-CSF were used to evaluate the relationship among these sources of Meg-CSA. Varying dilutions of IL-3 and GM-CSF antisera were tested in plasma clot cultures of normal human peripheral blood megakaryocyte progenitors optimally stimulated by either IL-3 (1 U/mL), GM-CSF (1 U/mL), PHA-LCM (2.5% to 5% vol/vol), or aplastic human serum (10% vol/vol). IL-3 antiserum at dilutions up to 1/2,000 totally abrogated megakaryocyte colony growth stimulated by IL-3. A 1/500 dilution of GM-CSF antiserum completely eliminated GM-CSF-induced megakaryocyte colony development. A combination of anti-IL-3 and anti-GM-CSF, each at a 1/500 dilution, inhibited all megakaryocyte colony growth stimulated by optimal concentrations of IL-3 and GM-CSF together. There was no neutralizing crossreactivity between the IL-3 and GM-CSF antisera. At maximally neutralizing concentrations, IL-3 antiserum inhibited 66% of the megakaryocyte colony growth stimulated by PHA-LCM. Residual megakaryocyte colony growth was eliminated by the addition of a 1/500 dilution of anti-GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, Miriam Hospital, Providence, RI 02906.
E M
EM
Mazur
J L
JL
Cohen
J
J
Newton
P
P
Sohl
A
A
Narendran
T G
TG
Gesner
R A
RA
Mufson
D000741:Anemia, Aplastic / Q000097:blood; D002455:Cell Division; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000276:immunology / Q000494:pharmacology*; D058851:GPI-Linked Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000276:immunology / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007377:Interleukin-3 / Q000276:immunology / Q000494:pharmacology*; D008214:Lymphocytes / Q000378:metabolism*; D008533:Megakaryocytes / Q000166:cytology*; D008562:Membrane Glycoproteins; D000090204:Mesothelin; D010835:Phytohemagglutinins / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D058851:GPI-Linked Proteins; D006133:Growth Substances; D007106:Immune Sera; D007377:Interleukin-3; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D011506:Proteins; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000090204:Mesothelin