Regulation of gene expression of M-, G-, GM-, and multi-CSF in normal and malignant hematopoietic cells.

摘要: Colony stimulating factors (CSFs) are produced by a variety of cell types, including T-lymphocytes (T cells) and mononuclear phagocytes; both types known to cooperatively interact elaborate CSFs, although the specific cellular source CSF species mechanisms intercellular communications in this regard poorly understood. In report, we investigate origin various peripheral blood cells (PBMC), purified T-lymphocyte monocyte (Mo) populations. Furthermore, assess conditions required for stimulation cultures express messenger RNAs (mRNAs) proteins. absence exogenous activation stimuli, human PBMC, T Mo failed produce transcripts macrophages (M-CSF or CSF-1), granulocytes (G-CSF), granulocytes/macrophages (GM-CSF), multilineage (multi-CSF Il-3). However, after with phorbol myristate acetate (PMA) phytohemagglutinin (PHA), mRNAs M-, G-, GM-CSF, multi-CSF became detectable PBMC as early 6 hours initiation cultures. Identical culture resulted synthesis M-CSF mRNA Mo, whereas GM-CSF mRNA. More physiologically, when were activated interferon (IFN)-gamma tumor necrosis factor-alpha (TNF-alpha) stimulated an Mo-independent pathway, that is via triggering 50 kd sheep erythrocyte receptor protein employing monoclonal antibodies (mo ab) Tll-2- Tll-3- defined epitopes, similar kinetics expression obtained. Similarly, interleukin-1 (Il-1) receptive Il-1, transcribed functionally active multi-CSF. Maximum peak activity GM-, secretion was identical all investigated, occurred 48-72 induction. Constitutive CSFs not found unactivated normal hematopoietic was, however, frequently observed blast populations patients acute myeloblastic leukemia. Of 49 AML samples, 15 revealed G-CSF transcripts; 11, mRNA; samples synthesized Employing bioassays, 12 G-CSF-mRNA-producing populations, 8 11 GM-CSF-mRNA-producing 1 M-CSF-mRNA-synthesizing demonstrated release respective into their supernatants.(ABSTRACT TRUNCATED AT 400 WORDS)