Production of interleukin 1 beta by human hematopoietic progenitor cells

• Published in: The Journal of clinical investigation 1996-04, Vol.97 (7), p.1666-1674
• Main Authors: Watari, K, Mayani, H, Lee, F, Dragowska, W, Lansdorp, P M, Schrader, J W
• Format: Article
• Language: English
• ISSN: 0021-9738
• DOI: 10.1172/JCI118593

The production of interleukin 1 beta (IL-1 beta ) by human hematopoietic stem /progenitor cells was studied to explore the concept that these cells are not merely responders to stimuli from their microenvironment, but can themselves produce a powerful biomodulator. Cells with a CD34 super(+) CD45RA super(lo) CD71 super(lo) phenotype were purified from human umbilical cord blood and cultured one per well in serum-free medium with a mixture of cytokines. Cells that had divided over 2-5 d to form doublets were identified and the daughter cells were studied individually. 91% (460/506) of daughter cells had clonogenic potential. Analysis of these individual daughter cells by reverse transcription-polymerase chain reaction showed that 29% of them (14/48) were positive for IL-1 beta mRNA. One of the cells that was strongly positive for IL-1 beta mRNA had a sibling that generated 366,000 cells of multiple lineages after 14 d. IL-1 beta converting enzyme mRNA, which is necessary to produce IL-1 beta , was also detected by reverse transcription-polymerase chain reaction at the single-cell level. Moreover, enzyme immunoassay for mature secreted IL-1 beta in culture supernatants demonstrated the production of IL-1 beta protein by these cells. This was confirmed by fluorescent immunostaining of the cells for human IL-1 beta which showed a significant portion of positive cells. Taken together, the results demonstrate the capacity of early hematopoietic cells to synthesize IL-1 beta . The capacity of human hematopoietic stem/progenitor cells to produce IL-1 beta may be involved in regulation of their proliferation and differentiation under certain circumstances and dysregulation of this process may be modified in leukemogenesis.