Leukocyte colony-stimulating factor and inhibitor activity.

Native and density gradient separated rat peritoneal exudate cells were evaluated for both their capacity to stimulate granulocyte colony formation and their ability to inhibit colony growth in vitro. Granulocyte colony-stimulating factor (CSF) was primarily elaborated by monocytes and macrophages; neutrophils showed only minimal stimulatory activity. In contrast, freeze-thawed extracts of both monocyte-macrophage and granulocyte fractions were markedly inhibitory to colony growth using a standard L-cell-derived CSF. Characterization of the inhibitory material indicated it to be a low molecular weight, nonlipid, heat-stable substance. In addition to peritoneal leukocytes, other tissues including lymph node, thymic and splenic lymphocytes, liver, kidney, and skeletal muscle also contained inhibitory materials. These observations suggest that granulopoiesis, as assessed by in vitro culture techniques, is not influenced solely by a simple feedback loop; rather, leukocytic elements, as well as other tissues, appear to contain and release both stimulatory and inhibitory factors.