A functional granulocyte colony-stimulating factor receptor is required for normal chemoattractant-induced neutrophil activation
Tomoko Betsuyaku, … , Kouji Matsushima, Daniel C. Link
Tomoko Betsuyaku, … , Kouji Matsushima, Daniel C. Link
Published March 15, 1999
Citation Information: J Clin Invest. 1999;103(6):825-832. https://doi.org/10.1172/JCI5191.
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Article

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

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.

Authors

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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Figure 8

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IL-8–induced PMN emigration into the skin. Interleukin-8 (IL-8; 50 ng) o...
IL-8–induced PMN emigration into the skin. Interleukin-8 (IL-8; 50 ng) or buffer alone was injected intradermally into wild-type or G-CSFR–deficient mice (G-CSFR–/–). Four hours later, the skin at the injection site was excised and homogenized, and protein extracts were analyzed for MPO activity as described in Methods. MPO content is expressed as the relative MPO activity (OD450) per milligram of protein. Six wild-type and nine G-CSFR–deficient mice were analyzed. Data represent the mean ± SD. *P <0.05 compared with buffer alone injected skin. MPO, myeloperoxidase.