Regulation of granulopoiesis: The lactoferrin controversy

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    The role of Lf in regulating steady-state granulopoiesis has not been established with absolute certainty. A number of technical problems have been encountered in a number of laboratories. For example, in our laboratory, results can be highly variable. Occasionally, we see no effect at all, results we have been able to trace to endotoxin contamination in some cases, but that in others seem to reflect our choice of the IL-1 target cell. For example, when cultured human fibroblasts are exposed to conditioned medium from Lf treated monocytes, they consistently produce less CSA, but when endothelial cells are used, the cells sometimes produce less CSA, and other times do not. Although it is likely that this reflects the ability of the endothelial cell to produce its own IL-1, we are not yet sure that we will be able to explain each failure we have seen with endothelium. A number of other questions remain. For example, if CSA release is only inhibited by 50% Lf, why does the cycling progenitor fraction decline so substantially? Which of the CSFs and interleukins are affected by Lf? Are only those factors with granulopoietic activity inhibited? To what extent are these questions or any others related to the biologic activity of Lf addressed by the preceding work? Naturally, this decision is the reader's. I argue that the conclusions drawn by Sawatzki and Rich have emerged from studies plagued with numerous pitfalls and misunderstandings. The authors fail to distinguish between steady-state phagocyte production and induced granulopoietic hyperplasia, fail to evenhandedly interpret their own data (which, at least in my view, does indeed show that Lf actually inhibits CSA release by bone marrow cells), fail to recognize technical pitfalls (e.g., polymerization), fail to demonstrate that the observed stimulatory effects were inhibitable by anti-murine Lf antibodies, fail to measure the proliferative activity of CFU-GM in the treated and untreated animals, and have inadequately considered the current state of knowledge on either the complexities of hematopoietic regulation or Lf's mechanism of action, knowledge that would, for example, have predicted that endotoxin-stimulated animals would be wholly resistant to Lf's inhibitory influence. For investigators involved in studies on hematopoiesis, the Lf mystery is far from solved.

    Original languageEnglish (US)
    Pages (from-to)386-399
    Number of pages14
    JournalBlood Cells
    Volume15
    Issue number2
    StatePublished - 1989

    Fingerprint

    Lactoferrin
    Interleukin-1
    Endotoxins
    Endothelial Cells
    Granulocyte-Macrophage Progenitor Cells
    Interleukins
    Hematopoiesis
    Phagocytes
    Conditioned Culture Medium
    Polymerization
    Bone Marrow Cells
    Endothelium
    Hyperplasia
    Monocytes
    Fibroblasts
    Research Personnel
    Antibodies

    ASJC Scopus subject areas

    • Hematology

    Cite this

    Regulation of granulopoiesis : The lactoferrin controversy. / Bagby, G. C.

    In: Blood Cells, Vol. 15, No. 2, 1989, p. 386-399.

    Research output: Contribution to journalArticle

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