GM‐CSF: Receptor structure and transmembrane signaling

Human granulocyte‐macrophage colony‐stmulating factor (GM‐CSF) both stimulates hematopoietic precursor cells to grow as well as enhances the function of mature effector cells, such as neutrophils, eosinophils and macrophages. All of the biological actions of GM‐CSF appear to be mediated via binding to a single class of high‐affinity receptors present on all responsive cells. Affinity cross‐linking experiments demonstrate that the same 98 kDa cross‐linked species seen on other GM‐CSF‐responsive cells is also detected on a choriocarcinoma cell line, JAR. However, JAR cells express significantly increased numbers (10,000 sites/cell) of low‐affinity (Kd ∼ 1.5 nM) GM receptors. The GM‐CSF receptor is a glycoprotein which binds to wheat germ agglutinin‐sepharose. It is dramatically downregulated on neutrophils by phorbol esters and formyl‐methionylleucine‐phenylalanine (fMLP), but not by phosphatidylinositol‐dependent phospholipase C. GM‐CSF primes neutrophils for enhanced response to secondary stimuli, such as ionophore and chemotactic factors. Specifically, GM‐CSF enhances ³H‐arachidonic acid release, synthesis of leukotriene B₄ and platelet activity factor in response to fMLP and the calcium ionophores.