Effects of human GM-CSF on neutrophil degranulation in vitro

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates multiple differentiated functions of mature neutrophils. Increased expression of leukocyte adhesion molecules and chemotactic receptors on GM-CSF-treated neutrophils suggested that GM-CSF may stimulate neutrophil degranulation. The effects of GM-CSF on neutrophil degranulation were assessed by quantitating the release of an exclusive component of the specific granules, vitamin B₁₂ binding protein. Incubation of neutrophils with GM-CSF alone resulted in a significant release of [⁵⁷Co]-vitamin B₁₂ binding protein quantitatively similar to that elicited by cytochalasin B or N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe) alone. In addition, cells preincubated with GM-CSF and subsequently stimulated with f-Met-Leu-Phe, platelet-activating factor, or the calcium ionophore, A23187, demonstrated enhanced degranulation, which greatly exceeded that produced by GM-CSF alone. These results demonstrate a small direct effect of GM-CSF on neutrophil degranulation, as well as enhanced degranulation in cells stimulated by chemotactic agents and calcium ionophore. Neutrophil degranulation in response to GM-CSF may be involved in the phlebitis associated with therapeutic administration of GM-CSF.