A functional granulocyte colony-stimulating factor receptor is required for normal chemoattractant-induced neutrophil activation

Tomoko Betsuyaku, Fulu Liu, Robert M. Senior, Jeffery S. Haug, Eric J. Brown, Samuel L. Jones, Kouji Matsushima, Daniel C. Link

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Abstract

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 β2-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.

Original languageEnglish
Pages (from-to)825-832
Number of pages8
JournalJournal of Clinical Investigation
Volume103
Issue number6
DOIs
Publication statusPublished - 1999 Mar

ASJC Scopus subject areas

  • Medicine(all)

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    Betsuyaku, T., Liu, F., Senior, R. M., Haug, J. S., Brown, E. J., Jones, S. L., Matsushima, K., & Link, D. C. (1999). A functional granulocyte colony-stimulating factor receptor is required for normal chemoattractant-induced neutrophil activation. Journal of Clinical Investigation, 103(6), 825-832. https://doi.org/10.1172/JCI5191