Modulation of mature human neutrophil function by colony-stimulating factors

Abstract

Colony-stimulating factors (CSFs) are glycoproteins which have been identified as being involved in the regulation of hematopoietic pathways. While all the cells of the blood are formed from the pluripotent stem cell, the various CSFs direct the proliferation and differentiation of committed cells in the macrophage-granulocyte cell series. These factors have been chemically characterized and they have recently been synthesized using recombinant DNA technology. While the CSFs were originally defined as stimulators of blood cell production, the availability of these factors in pure quantities has now made it possible to address the possible role of the CSFs in the regulation of the function of mature cells. In this study mature human polymorphonuclear leukocytes (PMNs) were treated with either recombinant human granulocyte colony-stimulating factor (rhG-CSF) or recombinant hum granuocyte marcophage colony-stimulating factor (rhGM-CSF). Function of the PMNs which were relevant to resistance to bacterial infection were then studied in order to determine the potential value of the CSFs as biological response modifiers. while rhG-CSF and rhGM-CSF did not affect the random motility, or chemkinesis, of the mature PMNs, they did bring about changes in the directed movement, or chemotaxis, of the cells. The hormones were able to act as chemoattractants and they also were able to inhibit the movement of the cells toward another chemoattractant agent. These properties of the hormones may be important in attracting PMNs to the site of infection and keeping them localized once they have arrived. No effects on the ability of the PMNs to degranulate or kill ingested Pseudomonas aeruginosa were observed. Evidence that the CSFs were interacting with the cells was also provided by microspectrophotometric analysis of deoxyribonucleic acid (DNA) template activity of treated cells. The increase in template activity is related to an increase in gene expression. These results provide further evidence of a possible role for the CSFs in the modulation of the function of mature neutrophils.