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

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

Research output: Contribution to journalArticle

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Abstract

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
Pages (from-to)397-426
Number of pages30
JournalBlood Cells
Volume10
Issue number2-3
StatePublished - 1984

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Lactoferrin
Histocompatibility Antigens Class II
Granulocyte-Macrophage Colony-Stimulating Factor
Granulocyte-Macrophage Progenitor Cells
Myeloid Progenitor Cells
Monocytes
U937 Cells
Erythroid Precursor Cells
Monoclonal Antibodies
Lymphocytes
Ferritins
acidic isoferritin
In Vitro Techniques
Blood Cells
Iron
Monocyte-Macrophage Precursor Cells
Myelopoiesis
Peritoneal Macrophages
Serum
Granulocytes

ASJC Scopus subject areas

  • Hematology

Cite this

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

Functional activities of acidic isoferritins and lactoferrin in vitro and in vivo. / Broxmeyer, Hal; Gentile, P.; Cooper, S.; Lu, L.; Juliano, L.; Piacibello, W.; Meyers, P. A.; Cavanna, F.

In: Blood Cells, Vol. 10, No. 2-3, 1984, p. 397-426.

Research output: Contribution to journalArticle

Broxmeyer, H, Gentile, P, Cooper, S, Lu, L, Juliano, L, Piacibello, W, Meyers, PA & Cavanna, F 1984, 'Functional activities of acidic isoferritins and lactoferrin in vitro and in vivo', Blood Cells, vol. 10, no. 2-3, pp. 397-426.
Broxmeyer H, Gentile P, Cooper S, Lu L, Juliano L, Piacibello W et al. Functional activities of acidic isoferritins and lactoferrin in vitro and in vivo. Blood Cells. 1984;10(2-3):397-426.
Broxmeyer, Hal ; Gentile, P. ; Cooper, S. ; Lu, L. ; Juliano, L. ; Piacibello, W. ; Meyers, P. A. ; Cavanna, F. / Functional activities of acidic isoferritins and lactoferrin in vitro and in vivo. In: Blood Cells. 1984 ; Vol. 10, No. 2-3. pp. 397-426.
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AU - Broxmeyer, Hal

AU - Gentile, P.

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AU - Juliano, L.

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