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Megakaryocyte induced fibroblast proliferation is enhanced by costimulation with IL-6/IL-3 and dependent on secretory

B Schmitz1, C Wickenhauser, J Thiele

  • 1Institute of Pathology, University of Cologne, Germany.

Leukemia Research
|August 24, 1999
PubMed

Insights

Megakaryocytes promote fibroblast growth, enhanced by interleukin-3 (IL-3). IL-6 combined with IL-3 boosts this effect, requiring direct cell contact for fibroblast proliferation, relevant to myelofibrosis.

Area of Science:

  • Hematology
  • Cell Biology
  • Oncology

Background:

  • Megakaryocytes from human bone marrow can promote fibroblast growth.
  • Interleukin-3 (IL-3) significantly enhances this megakaryocyte-driven fibroblast proliferation.
  • IL-3 stimulates megakaryocytes to release platelet-derived growth factor (PDGF) and transforming growth factor beta1 (TGF-beta1), key factors for fibroblast growth.

Purpose of the Study:

  • To investigate the in vitro effects of stem cell factor (SCF), IL-6, and leukemia inhibitory factor (LIF) on megakaryocyte-dependent fibroblast proliferation.
  • To elucidate the mechanisms underlying the synergistic effects of IL-3 and IL-6 on fibroblast growth.
  • To explore the role of cell-to-cell contact in megakaryocyte-fibroblast interactions.

Main Methods:

  • Coculture assays involving human bone marrow-derived megakaryocytes and fibroblasts.
  • Treatment with various cytokines including IL-3, IL-6, SCF, and LIF.
  • Transwell experiments to assess the impact of cell-to-cell contact inhibition.
  • Measurement of PDGF and TGF-beta1 secretion.

Main Results:

  • SCF, IL-6, and LIF alone did not enhance megakaryocyte-dependent fibroblast proliferation.
  • The combination of IL-6 and IL-3 significantly enhanced fibroblast proliferation beyond IL-3 alone.
  • This enhanced proliferation was not due to increased PDGF/TGF-beta1 secretion.
  • Inhibition of cell-to-cell contact using transwell inserts markedly impaired fibroblast growth in IL-3/IL-6 treated cocultures.

Conclusions:

  • Direct cell-to-cell contact between megakaryocytes and fibroblasts is crucial for the proliferative effect, likely by maintaining local growth factor concentrations.
  • The synergistic effect of IL-3 and IL-6 on fibroblast proliferation is dependent on cell adhesion phenomena.
  • These findings are significant for understanding myelofibrosis development in chronic myeloproliferative disorders, given megakaryocyte hypersensitivity to IL-3 and abnormal IL-6 secretion.

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