RESUMO
We have previously demonstrated that purified human fibrinogen (Fg), a major plasma component removed during serum preparation, shows mitogenic properties towards lymphoma cells and normal human hematopoietic progenitors. Indeed, 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, that 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-quantitative 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. Fg behaves not as a "progression" factor but as a typical "competence" factor, which induces a faster and greater IL-6R expression in early human hematopoietic progenitors by cooperating with other cytokines.
Assuntos
Antígenos CD34/imunologia , Fibrinogênio/fisiologia , Regulação da Expressão Gênica/fisiologia , Células-Tronco Hematopoéticas/metabolismo , Interleucina-6/fisiologia , RNA Mensageiro/genética , Receptores de Interleucina-6/genética , Células-Tronco Hematopoéticas/imunologia , Humanos , Hibridização In SituRESUMO
Hematopoiesis is a remarkable cell-renewal process that leads to the continuous generation of large numbers of multiple mature cell types, starting from a relatively small stem cell compartment. A highly complex but efficient regulatory network is necessary to tightly control this production and to maintain the hematopoietic tissue in homeostasis. During the last 3 decades, constantly growing numbers of molecules involved in this regulation have been identified. They include soluble cytokines and growth factors, cell-cell interaction molecules, and extracellular matrix components, which provide a multifunctional scaffolding specific for each tissue. The cloning of numerous growth factors and their mass production have led to their possible use for both fundamental research and clinical application.