Human serum megakaryocyte colony-stimulating activity appears to be distinct from interleukin-3, granulocyte-macrophage colony-stimulating factor, and lymphocyte-conditioned medium

Abstract

Sera from patients with bone marrow megakaryocyte aplasia are a rich source of megakaryocyte colony-stimulating activity (Meg-CSA). Other biologic materials exhibiting Meg-CSA include phytohemagglutinin- stimulated human lymphocyte-conditioned medium (PHA-LCM), recombinant interleukin-3 (IL-3), and recombinant granulocyte macrophage colony- stimulating factor (GM-CSF). Neutralizing antisera to both recombinant IL-3 and GM-CSF were used to evaluate the relationship among these sources of Meg-CSA. Varying dilutions of IL-3 and GM-CSF antisera were tested in plasma clot cultures of normal human peripheral blood megakaryocyte progenitors optimally stimulated by either IL-3 (1 U/mL), GM-CSF (1 U/mL), PHA-LCM (2.5% to 5% vol/vol), or aplastic human serum (10% vol/vol). IL-3 antiserum at dilutions up to 1/2,000 totally abrogated megakaryocyte colony growth stimulated by IL-3. A 1/500 dilution of GM-CSF antiserum completely eliminated GM-CSF-induced megakaryocyte colony development. A combination of anti-IL-3 and anti- GM-CSF, each at a 1/500 dilution, inhibited all megakaryocyte colony growth stimulated by optimal concentrations of IL-3 and GM-CSF together. There was no neutralizing crossreactivity between the IL-3 and GM-CSF antisera. At maximally neutralizing concentrations, IL-3 antiserum inhibited 66% of the megakaryocyte colony growth stimulated by PHA-LCM. Residual megakaryocyte colony growth was eliminated by the addition of a 1/500 dilution of anti-GM-CSF.

The Platelet Count in Carcinoma of the Lung and Colon

“…Interestingly, several factors known to stimulate thrombocytopoiesis are known to also stimulate proliferation of other marrow cell lines (10,19) and fibrinogen synthesis (40--42). Several different cell types, including macrophages, lymphocytes, and endothelial cells are capable of contributing to relevant cytokines (19,43,44). Alternatively, it is possible that the increased platelet count in malignancy may, at least to some extent, represent shifts in megakaryocyte distributions which could lead to increased numbers of smaller platelets.…”

“…Taken together, existing data suggest that multiple hematologic features of malignancy, including thrombocytosis, neutrophilia, anemia, and hyperfibrinogenemia may be explained (at least in part) by a response of the host (through activation of monocytes, lymphocytes, and other cells) to the tumor. We postulate that appropriate model systems for tumor cell production of marrow-stimulating cytokines by tumor cells (47)(48)(49) or by host cells that are activated in patients with cancer (19,44) may be useful in elucidating mechanisms of thrombocytosis in cancer.…”

Differences Between Peripheral Blood and Cord Blood in the Kinetics of Lineage‐Restricted Hematopoietic Cells: Implications for Delayed Platelet Recovery Following Cord Blood Transplantation

“…In order to stimulate MK formation, the cells were cultured in nontreated 24‐well plates in 1 ml of IMDM that contained 20% human serum and 10 ng/ml TPO, according to the slightly modified method of Mazur et al . [30]. TPO was added twice a week, and half the medium containing growth factors was changed on day 6.…”