STAT3 controls the neutrophil migratory response to CXCR2 ligands by direct activation of G-CSF-induced CXCR2 expression and via modulation of CXCR2 signal transduction

114Citations
Citations of this article
95Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Neutrophil mobilization, the release of neutrophils from the bone marrow reserve into circulating blood, is important to increase peripheral neutrophil amounts during bacterial infections. Granulocyte colony-stimulating factor (G-CSF) and chemokines, such as macrophage-inflammatory protein-2 (MIP-2; CXCL2), can induce neutrophil mobilization, but the mechanism(s) they use remain unclear. Signal transducers and activator of transcription 3 (STAT3) is the principal intracellular signaling molecule activated upon G-CSF ligation of its receptor. Using a murine model with conditional STAT3 deletion in bone marrow, we demonstrated previously that STAT3 regulates acute G-CSF-responsive neutrophil mobilization and MIP-2-dependent neutrophil chemotaxis. In this study, we show STAT3 is also necessary for MIP-2-elicited neutrophil mobilization. STAT3 appears to function by controlling extracellular signal-regulated kinase (ERK) activation, which is important for MIP-2-mediated chemotaxis. In addition, we demonstrate that G-CSF stimulates the expression of the MIP-2 receptor via STAT3-dependent transcriptional activation of Il8rb. G-CSF treatment also induces STAT3-dependent changes in bone marrow chemokine expression levels which may further affect neutrophil retention and release. Taken together, our study demonstrates that STAT3 regulates multiple aspects of chemokine and chemokine receptor expression and function within the bone marrow, indicating a central role in the neutrophil mobilization response. © 2010 by The American Society of Hematology.

References Powered by Scopus

G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4

1189Citations
N/AReaders
Get full text

STAT3 mutations in the hyper-IgE syndrome

1035Citations
N/AReaders
Get full text

Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist

954Citations
N/AReaders
Get full text

Cited by Powered by Scopus

JAK and STAT Signaling Molecules in Immunoregulation and Immune-Mediated Disease

925Citations
N/AReaders
Get full text

STAT3 signaling in immunity

518Citations
N/AReaders
Get full text

The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases

482Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Nguyen-Jackson, H., Panopoulos, A. D., Zhang, H., Li, H. S., & Watowich, S. S. (2010). STAT3 controls the neutrophil migratory response to CXCR2 ligands by direct activation of G-CSF-induced CXCR2 expression and via modulation of CXCR2 signal transduction. Blood, 115(16), 3354–3363. https://doi.org/10.1182/blood-2009-08-240317

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 45

70%

Researcher 13

20%

Professor / Associate Prof. 6

9%

Readers' Discipline

Tooltip

Agricultural and Biological Sciences 23

37%

Biochemistry, Genetics and Molecular Bi... 16

25%

Medicine and Dentistry 13

21%

Immunology and Microbiology 11

17%

Save time finding and organizing research with Mendeley

Sign up for free