Cytokine-mediated regulation of CXCR4 expression in human neutrophils

Abstract

Several lines of evidence have suggested that a CXC chemokine receptor 4 (CXCR4)/stromal cell-derived factor-1 [SDF-1; CXC chemokine ligand 12 (CXCL12)] pair is involved in baseline trafficking of leukocytes into extravascular tissues and that modulation of surface CXCR4 expression may represent an alternative mechanism for control of cell-specific biological responses to SDF-1/CXCL12. We explored the regulation of CXCR4 expression by cytokines in polymorphonuclear neutrophils (PMNs). No significant surface expression of CXCR4 in freshly isolated PMNs was detected, but expression became apparent gradually during incubation. SDF-1α/CXCL12 initiated Ca2+ mobilization and migratory responses in 20 h cultured PMNs. The surface CXCR4 expression was suppressed most potently by interferon-γ (IFN-γ). IFN-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF also inhibited spontaneous CXCR4 expression. Real-time, quantitative PCR experiments revealed that a spontaneous increase and an IFN-γ-mediated decrease in surface CXCR4 paralleled changes in the CXCR4 mRNA level. These results on PMNs support the argument that the SDF-1 (CXCL12)/CXCR4 system is regulated by cell type-specific mechanisms.

Ubiquitin is a versatile scaffold protein for the generation of molecules withde novo binding and advantageous drug‐like properties

“…by diapedesis induced by inflammatory reactions do not occur. In addition, the endogenous level of several pro‐inflammatory cytokines known to interfere with the regulation of CXCR4[95–97] were not influenced by ubiquitin treatment.…”

Deciphering the Effects of 2D Black Phosphorus on Disrupted Hematopoiesis and Pulmonary Immune Homeostasis Using a Developed Flow Cytometry Method

“…CXCL1, CXCL2/3, CCL3, and keratinocyte-derived chemokine (KC) could mediate the recruitment of NEs to the lungs during inflammation. − B cell-attracting chemokine (BCA)-1, choline kinase (CK)­β, CXCL9, and CXCL10 can mediate the trafficking of LYs into the inflamed sites. , In addition, cytokines might also play important role in the distinct effects of two BPs. The surface CXCR4 expression could be suppressed by G-CSF, GM-CSF, IFN-α, and IFN-γ, , probably attributed to the decreased expression levels of CXCR4 on NEs induced by L-BP. Regarding the regulation of hematopoiesis, multiple cytokines, including colony-stimulating factors (CSFs), transforming growth factor (TGF)­β, and IL-6 could stimulate hematopoiesis, which has been extensively studied .…”

“…82,83 In addition, cytokines might also play important role in the distinct effects of two BPs. The surface CXCR4 expression could be suppressed by G-CSF, GM-CSF, IFN-α, and IFN-γ, 84,85 probably attributed to the decreased expression levels of CXCR4 on NEs induced by L-BP. Regarding the regulation of hematopoiesis, multiple cytokines, including colony-stimulating factors (CSFs), transforming growth factor (TGF)β, and IL-6 could stimulate hematopoiesis, which has been extensively studied.…”

Neutrophil sub-types in maintaining immune homeostasis during steady state, infections and sterile inflammation

“…Primed neutrophils from RA secreted cytokines such as B cell-activating factor (BAFF) and RANKL which activated B cells, osteoclasts and CD4 + T cells [ 113 , 114 ]. Cytokines including GM-CSF, IL-8 and TNF-α delayed neutrophil apoptosis and primed neutrophils to release granules in the synovial cavity [ 115 ]. RA neutrophils expressed high concentrations of elastase, gelatinase and collagenase responsible for tissue and cartilage damage [ 116 ].…”