Activation of neutrophils by granulocyte-macrophage colony-stimulating factor.

A hypothetical pathway of GM-CSF-induced signaling in human neutrophils is presented in Figure 4. The earliest postreceptor events leading to activation of cellular kinases and phosphorylation of c-raf on tyrosine and serine remain a mystery. It is conceivable that downstream events such as the production of LTB4 and PAF as well as other autocrine or paracrine activators of neutrophil-activation function may be involved in neutrophil activation and priming, or they may be downstream events irrelevant in the signaling cascade. The association of GM-CSF signaling and G-proteins, PLD, c-raf, tyrosine kinases, and the Na+/H+ antiport remain poorly understood.