Functional and biochemical characterization of a novel human macrophage-derived negative regulator of haematopoiesis

It is believed that haematopoiesis is regulated by both positive and negative signals derived from the marrow microenvironment, which includes macrophages. The identity and mechanism of action of the proteins mediating negative regulation is an area of active investigation. We report here the identification and initial characterization of a novel suppressor of early haematopoietic progenitors, designated NRH (for Negative Regulator of Haematopoiesis), isolated from the recently established human macrophage line 2MAC. The mechanism of NRH suppression appears to involve a marked decrease in the cycling of early progenitor cells. NRH activity was shown to be reversible and to correspond to an acidic, heparin-binding glycoprotein with a molecular weight of approximately 20,000 daltons (~ 20 kDa). By exploiting lectin specificity, hydrophobic interaction, and heparin affinity, we have developed a procedure for the rapid isolation of highly purified NRH from 2MAC-conditioned medium. By a number of functional and biochemical criteria, NRH appears to represent a novel macrophage-derived negative regulator of haematopoiesis which may have future application in certain clinical settings as a chemoprotectant of primitive haematopoietic cells.