The integrin α9β1 contributes to granulopoiesis by enhancing granulocyte colony-stimulating factor receptor signaling

The integrin alpha 9 beta 1 is widely expressed on neutrophils, smooth muscle, hepatocytes, endothelia, and some epithelia. We now show that mice lacking this integrin have a dramatic defect in neutrophil development, with decreased numbers of granulocyte precursors in bone marrow and impaired differentiation of bone marrow cells into granulocytes. In response to granulocyte colony-stimulating factor (G-CSF), alpha 9-deficient bone marrow cells or human bone marrow cells incubated with alpha 9 beta 1-locking antibody demonstrated decreased phosphorylation of signal transducer and activator of transcription 3 and extracellular signal-regulated protein kinase. These effects depended on the alpha 9 subunit cytoplasmic domain, which was required for formation of a physical complex between alpha 9 beta 1 and ligated G-CSF receptor. Integrin alpha 9 beta 1 was required for granulopoiesis and played a permissive role in the G-CSF-signaling pathway, suggesting that this integrin could play an important role in disorders of granulocyte development and other conditions characterized by defective G-CSF signaling.