Functional activities of acidic isoferritins and lactoferrin in vitro and in vivo

H. E. Broxmeyer, P. Gentile, S. Cooper, L. Lu, L. Juliano, W. Piacibello, P. A. Meyers, F. Cavanna

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The functional activities of acidic isoferritins (AIF) and lactoferin (LF) were evaluated. The inhibitory activity of AIF (AIFIA) was inactivated by preincubation with a monoclonal antibody (2A4) against AIF, but AIFIA was not inactivated by another monoclonal antibody against AIF (1C5), by a monoclonal antibody (3A5) against basic isoferritins, or by a heteroantiserum (LFT) against basic isoferritins. Monoclonal 2A4 also inactivated the inhibitory activity against colony formation by granulocyte-macrophage (CFU-GM) progenitor cells that was constitutively released by human monocytes or induced by human monocytes in the presence of OKT4+ lymphocytes. In addition to OKT4+ lymphocytes, the release of AIFIA from human monocytes was modulated by iron-saturated human LF and OKT8+ lymphocytes, both of which suppressed the release of AIFIA. Evidence for the physiologic relevance of AIF as a regulator of myelopoiesis was presented, in that human AIF suppressed the numbers of CFU-GM, BFU-E, and CFU-GEMM per femur and the cycling status of these cells in mice recovering from a sublethal dosage of Cytoxan. Abnormalities in LF and AIF interactions were found with cells from a pediatric patients with neutrophilia of unknown etiology that were consistent with the disease manifestations of neutrophilia. Polymorphonuclear neutrophils (PMN) from the patient contained low levels (1%-10% of control) of immunologically reactive LF and the LF found was ineffective as a suppressor molecule for the release of GM-CSF from normal mononuclear blood cells. In addition, the patient's GM-CSF releasing mononuclear blood cells were insensitive to the suppressive effects of purified LF, and colony formation by the patient's CFU-GM, but not BFU-E or CFU-GEMM, were insensitive to the suppressive effects of purified AIF. When the activity of purified AIF was assessed against mouse bone marrow cells under serum-free conditions, it was apparent that serum was not needed for the suppressive activity of AIF. Human monoblast cell line U937 was found to be a good model in vitro for the actions of LF and AIF; U937 cells induced for a Ia-antigens by human gamma interferon were separated into populations of Ia-antigen+ and Ia-antigen- cells by fluorescence activated cell sorting (FACS), and LF and AIF suppressed colony formation only by the Ia-antigen+ U937 cells. A comparative analysis of bovine and human LF against release of GM-CSF from human mononuclear cells demonstrated that both were active in their iron-saturated form. Human LF was more active than bovine LF, although concentrations as low as 10-12 to 10-13 M bovine LF were effective. Bovine LF was also able to decrease release of GM-CSF from resident mouse peritoneal macrophages.

Original languageEnglish (US)
Pages (from-to)397-426
Number of pages30
JournalBlood Cells
Issue number2-3
StatePublished - 1984

ASJC Scopus subject areas

  • Hematology

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    Broxmeyer, H. E., Gentile, P., Cooper, S., Lu, L., Juliano, L., Piacibello, W., Meyers, P. A., & Cavanna, F. (1984). Functional activities of acidic isoferritins and lactoferrin in vitro and in vivo. Blood Cells, 10(2-3), 397-426.