Qualitative functional deficiency of affinity-purified lactoferrin from neutrophils of patients with chronic myelogenous leukemia, and lactoferrin/H-ferritin-cell interactions in a patient with lactoferrin-deficiency with normal numbers of circulating leukocytes.
The iron-binding proteins lactoferrin (LF) and H-ferritin have been implicated in the negative regulation of myelopoiesis in vitro and in vivo. The present studies evaluated the functional activity of affinity-purified LF from polymorphonuclear neutrophils (PMN) of patients with chronic myelogenous leukemia (CML) and LF/H-ferritin-cell interactions in a nonleukemic patient with LF deficiency with normal levels of circulating blood leukocytes. Affinity-purified CML-PMN-LF was found to be qualitatively deficient as a suppressor of the release of colony-stimulating factors from mononuclear blood cells, adding to previous information from our group documenting defective LF-cell interactions in CML. LF was detected by immunoradiometric assay in PMN of the patient with LF deficiency, but at a much lower level than normal. This LF was found, however, to be active as a suppressor molecular against the patient's cells and normal donor cells. Patient cells were as responsive as normal cells to effects of purified milk LF. Decreased LF levels in this patient were associated with increased levels of monocyte H-ferritin inhibitory activity, consistent with the known suppressive effects in vitro of LF on H-ferritin release from monocytes. Patient marrow hematopoietic progenitor cells were as responsive as progenitors from normal donors to suppression by purified H-ferritin and prostaglandin E1. These results are consistent with a role of LF and H-ferritin in the control of myelopoiesis in this patient.
Broxmeyer
H E
HE
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis.
Bicknell
D C
DC
Cooper
S
S
Sledge
G
G
Williams
D E
DE
McGuire
W A
WA
Coates
T D
TD
D000527:Alprostadil / Q000494:pharmacology; D002846:Chromatography, Affinity; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D003864:Depression, Chemical; D015232:Dinoprostone / Q000494:pharmacology; D005293:Ferritins / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007781:Lactoferrin / Q000097:blood / Q000172:deficiency* / Q000302:isolation & purification / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000737:chemistry*; D012636:Secretory Rate / Q000187:drug effects
D003115:Colony-Stimulating Factors; D005293:Ferritins; D007781:Lactoferrin; D000527:Alprostadil; D015232:Dinoprostone