Stimulation of Human Haemopoietic Cells by Colony Stimulating Factors: Adherent Cell Dependent Colony Stimulating Activity in Human Serum

Abstract

The number of granulocyte-macrophage clones formed in agar culture of bone marrow is dependent on levels of colony stimulating activity (CSA), a proposed in vivo hemopoietic regulator. A dose-response relationship for stimulation of human hemopoietic cells by CSA is demonstrated, which could be explained by thresholds of stimulation to cell division following a normal distribution. A simple method for the comparison of activities of test and control sources of CSA is presented. The apparent potentiating effect of the addition of 2 sources of CSA is explained by this dose-response relationship. Hemopoietic cells from patients with chronic granulocytic or acute myeloid leukemia showed the same dose-response relationship. CSA levels in normal human sera were greatly reduced by assay in the absence of adequate numbers of bone marrow adherent cells (cells adherent to nylon or plastic) or peripheral blood leukocytes, suggesting the presence of 2 kinds of CSA in human serum, 1 dependent on the presence of bone marrow adherent cells and 1 effective in their absence. Reduction of numbers of nonspecific esterase positive cells in the bone marrow sample correlated with reduction in the stimulating effect of serum. In all sera tested, adherent cell dependent CSA was the major component.