Treatment of human bone marrow with recombinant placenta immunoregulator ferritin results in myelopoiesis and T-cell suppression through modulation of the cytokine-chemokine networks.
OBJECTIVE
Placenta immunomodulator ferritin (PLIF) is a cloned human chimeric ferritin H chain with a novel non-ferritin C-terminal 48 amino acid sequence (C48). Recombinant PLIF-C48 exhibited cell-mediated immunosuppression. The aim of the current study was to investigate the regulatory effects of native placental ferritin (PLF), recombinant PLIF, and C48 on hematopoiesis of human bone marrow (BM).


METHODS
BM mononuclear cells (BM-MNCs) and CD34(+) selected cells were treated in vitro with either PLF, PLIF, or C48 without and in combination with granulocyte (G)-monocyte (M) colony-stimulating factor (GM-CSF) and subjected to hematopoietic progenitor cell assay. Cytokines and chemokines secreted by the treated cells were evaluated in culture supernatant using antibody array assays to determine mechanism of action.


RESULTS
In vitro treatment of BM-MNCs with PLF, PLIF, or C48 induced significant growth of myeloid colonies and when mixed with GM-CSF or Granulocyte-Colony Stimulating Factor (G-CSF) exhibited additive enhanced colony forming units-granulocyte monocyte growth. Yet, C48 treatment of selected CD34(+) cells did not yield colony formation and did not affect their response to GM-CSF. Treatment of BM-MNCs with C48 for 48 hours induced secretion of marked levels of GM-CSF, interleukin (IL)-6, IL-1, and IL-10. These cytokines were secreted primarily by C48-treated BM adherent cells and partly by nonadherent cells, whereas the CD34(+) selected cells secreted IL-6 only.


CONCLUSIONS
C48-PLIF enhancement of myelopoiesis resulted from cross talk between BM accessory cells and progenitor cells. The differential PLIF-C48 effects (i.e., myeloid progenitor cell growth and T-cell suppression) are due to their effect on the cytokine-chemokine networks.
Moroz
Chaya
C
Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Sackler School of Medicine, Tel-Aviv University, Petach-Tikva, Israel. hmoroz@post.tau.ac.il
Grunspan
Anna
A
Zahalka
Muayad A
MA
Traub
Leonid
L
Kodman
Yona
Y
Yaniv
Isaac
I
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000595:Amino Acid Sequence; D018952:Antigens, CD34 / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism*; D005293:Ferritins / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D038042:Myelopoiesis / Q000187:drug effects*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D018952:Antigens, CD34; D018925:Chemokines; D016207:Cytokines; D010446:Peptide Fragments; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005293:Ferritins