Specific binding sites for H-ferritin on human lymphocytes: modulation during cellular proliferation and potential implication in cell growth control.
Interactions between human recombinant H- and L-ferritins and human lymphocytes were studied in vitro by direct binding assays and by flow cytometry. L-ferritin did not cause detectable specific binding, whereas H-ferritin showed a specific and saturable binding that increased markedly in phytohemagglutinin (PHA)-stimulated cells. This ferritin bound up to 30% of CD4+ and CD8+ T-lymphocytes and most B cells, indicating that expression of ferritin binding sites is not related to cell lineage or function. Dual-color flow cytometry experiments showed that ferritin binding sites were present on cells expressing the proliferation markers HLA-DR, MLR3, interleukin 2 (IL-2), and transferrin receptors (Tf-R). In addition, after PHA induction, the time course of the expression of H-ferritin binding sites was similar to those of the above proliferation markers. Ferritin binding sites were observed in lymphocytes at all cell cycle phases, including the early S-phase. H-Ferritin at nanomolar and picomolar concentrations had an inhibitory effect on PHA-induced blastogenesis. We propose that H-ferritin binding sites behave like proliferation markers, with the unusual function of downregulating proliferation.
Fargion
S
S
Institute of Internal Medicine, Milan, Italy.
Fracanzani
A L
AL
Brando
B
B
Arosio
P
P
Levi
S
S
Fiorelli
G
G
D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000378:metabolism; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D005293:Ferritins / Q000378:metabolism* / Q000494:pharmacology; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis; D007700:Kinetics; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis; D010835:Phytohemagglutinins / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell; D011990:Receptors, Transferrin / Q000032:analysis; D011994:Recombinant Proteins / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
D000954:Antigens, Surface; D006684:HLA-DR Antigens; D007376:Interleukin-2; C059122:MLR3 activation antigen; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D005293:Ferritins