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Influence of cytokines (IL‐1α, IL‐3, IL‐11, GM‐CSF) on megakaryocyte‐fibroblast interactions in normal human bone marrow
Author(s) -
Schmitz Beate,
Thiele Juergen,
Witte Oliver,
Kaufmann Regina,
Wickenhauser Claudia,
Fischer Robert
Publication year - 1995
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.1995.tb00229.x
Subject(s) - megakaryocyte , cytokine , fibroblast , platelet derived growth factor receptor , growth factor , granulocyte macrophage colony stimulating factor , bone marrow , interleukin 3 , immunology , biology , haematopoiesis , endocrinology , medicine , microbiology and biotechnology , t cell , in vitro , stem cell , immune system , receptor , antigen presenting cell , biochemistry
The evolution of myelofibrosis accompanying chronic myeloproliferative disorders (CMPDs) is often linked with megakaryopoiesis. However, it is not known whether or to what extent megakaryocytes of normal human bone marrow are capable of stimulating fibroblast growth. For this reason, an in vitro study was performed to elucidate possible cytokine‐dependent interactions between megakaryocytes and fibroblasts derived from healthy volunteers. Fibroblast growth was significantly promoted by the presence of megakaryocytes and modulated by additional application of various cytokines. While recombinant human (rh) interleukin (IL)‐1α had no obvious effect on fibroblast proliferation, a slight increase was detected on adding granulocyte‐macrophage colony stimulating factor (rhGM‐CSF). Application of rhIL‐3 caused a significant increase in the number of fibroblasts. In contrast, administration of rhIL‐11 suppressed the megakaryocyte‐dependent growth‐promoting effect and co‐stimulation with rhIL‐3 led to a significant decrease of fibroblast number in comparison to rhIL‐3‐stimulated co‐cultures. Inhibition of cell‐cell contact in unstimulated, as well as in rhIL‐3‐stimulated co‐cultures led to a conspicuous impairment of fibroblast growth. A similar effect was observed when neutralizing antibodies directed against platelet‐derived growth factor (PDGF) and transforming growth factor (TGF)β 1 were added to rhIL‐3‐stimulated cultures. Our findings are in keeping with the assumption that interactions between megakaryocytes and fibroblasts involve in cytokine‐mediated functional network regulated by factors such as spatial relationship, cytokine stimulation, and low concentrations of mediators, particularly PDGF and TGFβ. In this complex system rhIL‐3 seems to play a crucial role in the promotion of these various interrelationships.