Fibrinogen cooperates with cytokines to induce interleukin-6 receptor mRNAexpression in human hematopoietic CD34(+) progenitors

We have previously demonstrated that purified human fibrinogen (Fg), a majo r plasma component removed during serum preparation, shows mitogenic proper ties towards lymphoma cells and normal human hematopoietic progenitors. Ind eed, adding Fg with IL-3 to a serum-containing medium stimulates growth of human CD34(+) progenitors. In this report, we show in serum-free medium, th at this stimulating effect only occurs in the presence of IL-6, To clarify the cooperative effect between Fg and IL-6, the kinetics of IL-6 receptor ( IL-6R) mRNA expression in CD34(+) cells have been analyzed by semi-quantita tive in situ hybridization, In the presence of both IL-3 and Fg, more cells express IL-6R mRNA, and this expression per cell is significantly greater than with each factor added separately. These results suggest that Fg does not promote the growth of normal cells by itself, but sensitizes the cells to cytokines. Pg behaves not as a "progression" factor but as a typical "co mpetence" factor, which induces a faster and greater IL-6R expression in ea rly human hematopoietic progenitors by cooperating with other cytokines.