Heterogeneity of recombinant granulocyte-macrophage colony-stimulating factor-mediated enhancement of neutrophil adherence to endothelium.

Human recombinant (r) and chemically synthesized granulocyte-macrophage colony-stimulating factor (GM-CSF) was found to enhance the attachment of neutrophils to monolayers of human umbilical vein endothelial cells by direct action upon the neutrophil. Using synthetic peptides of GM-CSF with truncated amino and carboxy termini, a region between amino acids 14 and 24 was found to be essential for neutrophil attachment. In analysis of the response of neutrophils from individual donors, a heterogeneity in their capacity to respond to GM-CSF by increased adherence was observed. The level of response to GM-CSF did not depend on receptor number. However, a positive correlation (r = 0.58) was found between the ability to respond to GM-CSF and the level of response to tumor necrosis factor--suggesting a link between the responses of neutrophils to these two cytokines. The stimulation of neutrophil adhesiveness to endothelial cells by rGM-CSF and the heterogeneity in donor response may have important implications for the clinical administration of GM-CSF.