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Effects of rhG‐CSF, 5‐fluorouracil and extramedullary irradiation on murine megakaryocytopoiesis in vivo
Author(s) -
Scheding Stefan,
Media Joseph E.,
Kraut Michael,
Valdivieso Manuel,
Nakeff Alexander
Publication year - 1994
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 - 10.1111/j.1365-2141.1994.tb05107.x
Subject(s) - megakaryocytopoiesis , in vivo , fluorouracil , cancer research , irradiation , chemistry , microbiology and biotechnology , medicine , andrology , biology , chemotherapy , megakaryocyte , haematopoiesis , stem cell , genetics , physics , nuclear physics
Summary The aim of this study was to systematically characterize possible rhG‐CSF effects on the murine megakaryocyte‐platelet system (untreated and recovering from chemotherapy or extramedullary irradiation). In untreated, splenectomized male B 6 D 2 F 1 mice rhG‐CSF treatment (50μg/kg/d for up to 8d) markedly decreased femoral megakaryocytopoiesis. CFU‐Meg, small acetylcholinesterase‐positive (SAChE) cells, and megakaryocytes were significantly reduced to 35–70%: platelets, however, were not affected. Peripheral CFU‐Meg and CFU‐GM increased up to 200‐fold. Following a single injection of 5‐FU (150mg/kg) on day O, rhG‐CSF (50 μg/kg/d) on days 1–8 suppressed the megakaryocytopietic recovery as indicated by significantly lower platelet numbers on day 9. Granulopoietic recovery was accelerated by rhG‐CSF. When rhG‐CSF treatment was started on day 5, no beneficial effect on granulopoietic recovery was observed, but again platelet levels were significantly lower on day 9, indicating that within the first 4 d of rhG‐CSF application, recruitment or lineage competition was not a critical event. To test for the effects of extramedullary irradiation on circulating progenitors, mice pretreated with 50 μg/kg/d of rhG‐CSF for 8 d received irradiation to the chest with 500 cGy resulting in a substantial kill of circulating CFU‐Meg and CFU‐GM of up to 99%. However, this striking decrease of blood progenitors did not significantly affect their total body contents. This sutdy indicates that rhG‐CSF treatment can impair bone marrow megakaryocytopoiesis, which might be an important consideration for those clinical situations that carry a high potential for treatment‐induced thrombocytopenia.