| First Author | Betsuyaku T | Year | 1999 |
| Journal | J Clin Invest | Volume | 103 |
| Issue | 6 | Pages | 825-32 |
| PubMed ID | 10079103 | Mgi Jnum | J:53611 |
| Mgi Id | MGI:1332987 | Doi | 10.1172/JCI5191 |
| Citation | Betsuyaku T, et al. (1999) A functional granulocyte colony-stimulating factor receptor is required for normal chemoattractant-induced neutrophil activation. J Clin Invest 103(6):825-32 |
| abstractText | Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor that is widely used to treat neutropenia. In addition to stimulating polymorphonuclear neutrophil (PMN) production, G-CSF may have significant effects on PMN function. Because G-CSF receptor (G- CSFR)-deficient mice do not have the expected neutrophilia after administration of human interleukin-8 (IL-8), we examined the effect of the loss of G-CSFR on IL-8-stimulated PMN function. Compared with wild- type PMNs, PMNs isolated from G-CSFR-deficient mice demonstrated markedly decreased chemotaxis to IL-8. PMN emigration into the skin of G-CSFR-deficient mice in response to IL-8 was also impaired. Significant chemotaxis defects were also seen in response to N-formyl- methionyl-leucyl-phenylalanine, zymosan-activated serum, or macrophage inflammatory protein-2. The defective chemotactic response to IL-8 does not appear to be due to impaired chemoattractant receptor function, as the number of IL-8 receptors and chemoattractant-induced calcium influx, actin polymerization, and release of gelatinase B were comparable to those of wild-type PMNs. Chemoattractant-induced adhesion of G-CSFR-deficient PMNs was significantly impaired, suggesting a defect in beta2-integrin activation. Collectively, these data demonstrate that selective defects in PMN activation are present in G- CSFR-deficient mice and indicate that G-CSF plays an important role in regulating PMN chemokine responsiveness. |
