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Persistent production of colony‐stimulating factor (CSF‐1) by cloned bone marrow stromal cell line D2XRII after X‐irradiation
Author(s) -
Naparstek Elizabeth,
Donnelly Thomas,
Shadduck Richard K.,
Waheed Abdul,
Wagner Katherine,
Kase Kenneth R.,
Greenberger Joel S.
Publication year - 1986
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041260311
Subject(s) - trypsinization , stromal cell , haematopoiesis , bone marrow , biology , cell culture , stem cell , immunology , cell growth , microbiology and biotechnology , cancer research , biochemistry , trypsin , genetics , enzyme
The adherent stromal layer in long‐term bone marrow cultures (LTBMC) provides the cellular environment necessary for the in vitro proliferation and differentiation of pluripotential hematopoietic stem cells. The role of humoral hematopoietic growth factors, colony‐stimulating factors (CSF) in the regulation of hematopoietic cell production in this system is poorly understood. We have recently isolated and cloned an adherent cell line, D2XRII, derived from murine LTBMC. Plateau phase 25 cm 2 cultures of 2 × 10 6 D2XRII cells in 8.0 ml produced CSF‐1 (M‐CSF) at around 100–150 units/0.1 ml medium. Following X‐irradiation there was a dose‐dependent decrease in the production of CSF‐1 to a plateau of 50% of control levels at 10,000 rad. Higher doses did not produce a further decrease. The X‐ray dose reducing CSF‐1 production to 50% was 100‐fold above the lethal dose as measured by clonagenic survival following trypsinization and replating. Trypsinized replated viable adherent but nondividing X‐irradiated D2XRII cells were maintained for up to 8 weeks after irradiation and demonstrated continuous production of CSF‐1. The data indicate significant divergence of two biologic effects of X‐irradiation on plateau‐phase marrow stromal cells: physiologic function of adherence and CSF‐1 production, versus proliferative integrity. This divergence of effects may be very relevant to understanding the mechanism of X‐irradiation‐associated marrow suppression and leukemogenesis.