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Interferon α2b directly induces fibroblast proliferation and transforming growth factor β secretion of macrophages
Author(s) -
Wickenhauser Claudia,
Schmitz Beate,
Selbach Barbara,
Brockbals Carina,
Manske Oliver,
Thiele Jürgen
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.02017.x
Subject(s) - megakaryocyte , fibroblast , macrophage , growth factor , haematopoiesis , platelet derived growth factor receptor , bone marrow , transforming growth factor , biology , platelet derived growth factor , cell growth , immunology , secretion , microbiology and biotechnology , cell culture , chemistry , in vitro , endocrinology , stem cell , biochemistry , genetics , receptor
To elucidate the effects of interferon α2b (IFN‐α) on normal human bone marrow, fibroblasts from patients without haematopoietic pathology were cultivated and used in stimulation experiments. Further, co‐cultures with highly enriched fractions of megakaryocytes and bone marrow macrophages were analysed. In this context, the influence of cell‐to‐cell interactions and humoral factors was determined in transwell and neutralization studies. Finally, secretion of platelet‐derived growth factor (PDGF) and transforming growth factor β1 (TGF‐β1) by single megakaryocytes and macrophages was examined by using the reverse haemolytic plaque assay (RHPA). Following these experimental designs, a direct proliferative activity of IFN‐α on bone marrow fibroblasts could be demonstrated. In the unstimulated co‐cultures, the megakaryocyte‐ but not the macrophage‐enriched fraction induced fibroblast growth and [ 3 H]‐thymidine uptake. This effect was dependent on cell‐to‐cell contact and also on the influence of TGF‐β and PDGF. In the megakaryocyte‐enriched co‐cultures, the fibroblast proliferation was not altered by IFN‐α, but in the macrophage fibroblast cultures addition of IFN‐α enhanced fibroblast growth and [ 3 H]‐thymidine uptake was distinctively higher than in the monocultures. This effect was not obvious in the transwell or neutralization experiments. Finally, IFN‐α treatment exerted a significantly elevated TGF‐β1 secretion in single macrophages. Our findings are in keeping with the assumption that several pathomechanisms participate in IFN‐α‐induced myelofibrosis, including direct and indirect effects.