The Integrin alpha9beta1 contributes to granulopoiesis by enhancing granulocyte colony-stimulating factor receptor signaling.
The integrin alpha9beta1 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), alpha9-deficient bone marrow cells or human bone marrow cells incubated with alpha9beta1-blocking antibody demonstrated decreased phosphorylation of signal transducer and activator of transcription 3 and extracellular signal-regulated protein kinase. These effects depended on the alpha9 subunit cytoplasmic domain, which was required for formation of a physical complex between alpha9beta1 and ligated G-CSF receptor. Integrin alpha9beta1 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.
Chen
Chun
C
Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, California 94158, USA.
Huang
Xiaozhu
X
Atakilit
Amha
A
Zhu
Quan-Sheng
QS
Corey
Seth J
SJ
Sheppard
Dean
D
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D016466:CHO Cells; D002454:Cell Differentiation / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism*; D006098:Granulocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D006410:Hematopoiesis / Q000276:immunology*; D015151:Immunoblotting; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection
D016023:Integrins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; C113256:integrin alpha 9 beta 1; D016179:Granulocyte Colony-Stimulating Factor