Chemokines: Roles in leukocyte development, trafficking, and effector function

Ono, Santa Jeremy; Nakamura, Toshio; Miyazaki, Dai; Ohbayashi, Masaharu; Dawson, Maria; Toda, Masako

doi:10.1067/mai.2003.1594

Cited by 223 publications

(171 citation statements)

References 117 publications

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…6b). Although the FPR and the IL-8 receptor both signal through pertussis toxin-sensitive G␣ i proteins (11,34), the angiotensin receptor signals predominantly through G␣ q (35) and the vasopressin receptor signals through G␣ s (36). These results suggest that apoptotic signaling in the absence of arrestins is mediated by a distinct subset of GPCRs, which signal through a wide variety of G protein subtypes.…”

Section: Gpcr-induced Apoptosis Is Executed Through the Mitochondrialmentioning

confidence: 99%

Arrestins Block G Protein-coupled Receptor-mediated Apoptosis

Revankar¹,

Vines²,

Cimino

et al. 2004

Journal of Biological Chemistry

119

107

View full text Add to dashboard Cite

G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) activate numerous cellular signals through the combined actions of G proteins, GPCR kinases, and arrestins. Although arrestins have traditionally been thought of as mediating GPCR desensitization, they have now been shown to play important roles in the internalization, trafficking, and signaling of many GPCRs. We demonstrate that in cells devoid of arrestins, the stimulation of numerous GPCRs including the N-formyl peptide receptor (FPR) initiates rapid cell rounding, annexin V positivity, and caspase activation followed by cell death. The apoptotic response is initiated by G protein signaling and involves activation of phosphoinositide 3-kinase, mitogen-activated protein kinases, and c-Src resulting in cytochrome c release from mitochondria and ultimately caspase 9 and caspase 3 activation. Reconstitution with either arrestin-2 or arrestin-3 is completely sufficient to prevent FPR-mediated apoptosis. Surprisingly, a non-desensitizing and non-internalizing mutant of the FPR is unable to initiate apoptosis, indicating that receptor phosphorylation and internalization, but not solely chronic activation due to a lack of desensitization, are critical determinants for the induction of apoptosis by the FPR. We further demonstrate that this response is not unique to the FPR with numerous additional GPCRs, including the V2 vasopressin, angiotensin II (type 1A), and CXCR2 receptors, capable of initiating apoptosis upon stimulation, whereas GPCRs such as the ␤ 2 -adrenergic receptor and CXCR4 are not capable of initiating apoptotic signaling. These data demonstrate for the first time that arrestins play a critical and completely unexpected role in the suppression GPCR-mediated apoptosis, which we show is a common consequence of GPCR-mediated cellular activation in the absence of arrestins.

show abstract

Section: Gpcr-induced Apoptosis Is Executed Through the Mitochondrialmentioning

confidence: 99%

Arrestins Block G Protein-coupled Receptor-mediated Apoptosis

Revankar¹,

Vines²,

Cimino

et al. 2004

Journal of Biological Chemistry

119

107

View full text Add to dashboard Cite

show abstract

“…Peripheral blood leukocytes and those found in secondary lymphoid organs are quite distinct and must express different chemokine receptors and adhesion molecules to be differentially localized during trafficking [7,20]. We examined sulfatide-induced CXCR4 upregulation on the heterogeneous population of leukocytes from various origins and observed detectable CXCR4 up-regulation on leukocytes isolated from the spleen, Peyer's patches, lymph nodes and bone marrow (data not shown); however, this increase was not as large as previously observed on human leukocytes from peripheral blood.…”

Section: Sulfatide Increases Cxcr4 Surface Expression On Murine Leukomentioning

confidence: 99%

“…Stromal-derived factor 1, renamed CXCL12, is a potent chemoattractant for a variety of cells including lymphocytes, monocytes, dendritic cells, and hematopoietic stem cells [3]. CXCL12 and its receptor CXCR4 play significant roles in immune and inflammatory responses, in lymphopoiesis, and in embryonic development; deletion of either CXCL12 or CXCR4 in rodent models is lethal [5,7]. Many studies have attributed an important role to CXCL12/CXCR4 signaling in migration and recruitment.…”

Section: Introductionmentioning

confidence: 99%

Up‐regulation of leukocyte CXCR4 expression by sulfatide: An L‐selectin‐dependent pathway on CD4⁺ T cells

et al. 2007

View full text Add to dashboard Cite

CXCR4 plays significant roles in immune and inflammatory responses and is important for selective recruitment of leukocytes. We previously showed that CXCR4 surface expression of human lymphocytes was affected by sulfatide, an in vivo ligand for L-selectin. Increased CXCR4 expression was shown to promote biologically relevant functions such as integrin-dependent adhesion and transmigration. Here, we show that sulfatide-induced CXCR4 up-regulation also occurs on other leukocyte subsets in humans and mice. B cells and CD4 + CD25 + T cells had the highest CXCR4 up-regulation after sulfatide stimulation. Transfection of L-selectin was sufficient for K562 cells to acquire sulfatide-induced CXCR4 up-regulation, while analysis of L-selectin knockout mice revealed that this response was critically L-selectin dependent only for CD4 + T cells, suggesting an alternative pathway in CD8 + T cells and B cells. Sulfatide triggered several intracellular signaling events in CD4 + T cells, but only tyrosine kinase activation, including members of the Src family, were essential for L-selectin to CXCR4 signaling. CXCR4 up-regulation was rapid, enhanced CXCL12-induced signaling and increased chemotaxis toward CXCL12, and therefore has potentially important roles in vivo. Thus, the response to CXCL12 depends in part on tissue expression of sulfatide and, specifically in CD4 + T cells, also depends on the surface level of L-selectin.

show abstract

“…Besides the classical Fc⑀RI-mediated mechanism, mast cells are also activated by chemokines (3,4). A superfamily of small, structurally related cytokine molecules, chemokines are characterized by their ability to affect trafficking of leukocytes.…”

mentioning

confidence: 99%

“…A superfamily of small, structurally related cytokine molecules, chemokines are characterized by their ability to affect trafficking of leukocytes. Some chemokines, such as CCL2/MCP-1 (monocyte chemotactic protein 1), CCL3/MIP-1␣ (macrophage inflammatory protein-1␣), CCL5/RANTES (regulated upon activation, normal T-cell expressed and secreted), and CCL11/eotaxin-1, have been reported to activate mouse, rat, or human mast cells (3)(4)(5)(6). Abundant expression of these CC chemokines and accumulation of leukocytes has also been observed in allergic inflammatory tissues (7)(8)(9).…”

mentioning

confidence: 99%

Evidence That Formation of Vimentin·Mitogen-activated Protein Kinase (MAPK) Complex Mediates Mast Cell Activation following FcεRI/CC Chemokine Receptor 1 Cross-talk

Toda

Kuo

Borman

et al. 2012

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: CC chemokine ligand 2 (CCL2) recruits leukocytes in inflammatory tissues. Results: Vimentin, a cytoskeletal protein, interacted with phosphorylated MAPKs, was critical for CCL2 production in mast cells activated via F⑀cRI and a CC chemokine receptor. Conclusion: Vimentin was involved in optimal CCL2 production in mast cells. Significance: This work contributes to understanding of mechanisms for chemokine production in mast cells, which are therapeutic targets for allergic inflammation.

show abstract

Chemokines: Roles in leukocyte development, trafficking, and effector function

Cited by 223 publications

References 117 publications

Arrestins Block G Protein-coupled Receptor-mediated Apoptosis

Arrestins Block G Protein-coupled Receptor-mediated Apoptosis

Up‐regulation of leukocyte CXCR4 expression by sulfatide: An L‐selectin‐dependent pathway on CD4⁺ T cells

Evidence That Formation of Vimentin·Mitogen-activated Protein Kinase (MAPK) Complex Mediates Mast Cell Activation following FcεRI/CC Chemokine Receptor 1 Cross-talk

Contact Info

Product

Resources

About

Chemokines: Roles in leukocyte development, trafficking, and effector function

Cited by 223 publications

References 117 publications

Arrestins Block G Protein-coupled Receptor-mediated Apoptosis

Arrestins Block G Protein-coupled Receptor-mediated Apoptosis

Up‐regulation of leukocyte CXCR4 expression by sulfatide: An L‐selectin‐dependent pathway on CD4+ T cells

Evidence That Formation of Vimentin·Mitogen-activated Protein Kinase (MAPK) Complex Mediates Mast Cell Activation following FcεRI/CC Chemokine Receptor 1 Cross-talk

Contact Info

Product

Resources

About

Up‐regulation of leukocyte CXCR4 expression by sulfatide: An L‐selectin‐dependent pathway on CD4⁺ T cells