PRODUCTION OF INTERLEUKIN-1-BETA BY HUMAN HEMATOPOIETIC PROGENITOR CELLS

The production of interleukin 1 beta (IL-1 beta) by human hematopoieti c 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 CD3 4(+) CD45RA(lo) CD71(lo) phenotype were purified from human umbilical cord blood and cultured one per well in serum-free medium with a mixtu re of cytokines, Cells that had divided over 2-5 d to form doublets we re identified and the daughter cells were studied individually, 91% (4 60/506) of daughter cells had clonogenic potential, Analysis of these individual daughter cells by reverse transcription-polymerase chain re action showed that 29% of them (14/48) were positive for IL-1 beta mRN A, 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 rea ction at the single-cell level, Moreover, enzyme immunoassay for matur e secreted IL-1 beta in culture supernatants demonstrated the producti on of IL-1 beta protein by these cells, This was confirmed by fluoresc ent immunostaining of the cells for human IL-1 beta which showed a sig nificant portion of positive cells, Taken together, the results demons trate the capacity of early hematopoietic cells to synthesize IL-1 bet a, The capacity of human hematopoietic stem/progenitor cells to produc e IL-1 beta may be involved in regulation of their proliferation and d ifferentiation under certain circumstances and dysregulation of this p rocess may be modified in leukemogenesis.