Chemokines and chemokine receptors in leukocyte trafficking

Olson, Timothy S.; Ley, Klaus

doi:10.1152/ajpregu.00738.2001

Cited by 585 publications

(467 citation statements)

References 184 publications

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“…In response to inflammatory stimuli, they migrate from the circulation to infected tissues, where they protect their host by phagocytosing, killing and digesting bacterial and fungal pathogens. 33,34 Many neutrophil functions are mediated by PtdIns(3,4,5)P3. For example, a variety of chemoattractants such as bacteria-released formyl-peptides, some complement fragments Interestingly, the InsP3 kinase is not constitutively active in neutrophils.…”

Section: Ins(1345)p4 and Insp3kb Regulate Innate Immunity Via Modumentioning

confidence: 99%

Regulation of innate immunity by inositol 1,3,4,5-tetrakisphosphate

2008

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Section: Ins(1345)p4 and Insp3kb Regulate Innate Immunity Via Modumentioning

confidence: 99%

Regulation of innate immunity by inositol 1,3,4,5-tetrakisphosphate

2008

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“…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%

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

et al. 2007

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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.

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“…Macrophages stimulated with CSF-1 show immediate cell polarization, actin reorganization, and migration to the CSF-1 secreting tumor cells [9]. Extensive studies have revealed the molecular mechanism of chemokine receptor, a subfamily of G-protein-coupled receptors, -mediated leukocyte trafficking during inflammation [10,11]. However, the signal transduction pathway that regulates CSF-1-induced macrophage migration is still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Akt2 is required for macrophage chemotaxis

Zhang

Guo

et al. 2009

Eur J Immunol

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Tumor-associated macrophages play an important role in tumorigenesis and metastasis. Trafficking of macrophages to the proximity of tumors is mediated by CSF-1, a growth factor. In this study, we investigated the role of PKB/Akt in CSF-1-induced macrophage migration. Disruption of Akt2 expression by small interference RNA impaired chemotaxis of both THP-1 cells and mouse peritoneal macrophages. Phosphorylation of PKCf, an essential component in chemotaxis signaling pathway, was reduced. LIMK/Cofilin, downstream of PKCf, regulated cytoskeleton rearrangement during cell migration. Disruption of Akt2 expression inhibited CSF-1-induced LIMK/Cofilin phosphorylation, which contributed to defects in actin polymerization and chemotaxis. Furthermore, MCP-1, a chemokine, -induced macrophage chemotaxis was also impaired. Taken together, our results demonstrated that Akt2 plays an essential role in both CSF-1-and chemokine-induced chemotaxis of macrophages.Key words: Chemokine . CSF-1 . Metastasis . Tumor-associated macrophages IntroductionChronicle inflammation promotes, sometimes even induces, tumorigenesis [1,2]. Tumor attracts macrophages and induces their differentiation by secreting . In comparison with conventional macrophages, tumor-associated macrophage (TAM) cells exhibit poor antigen-presenting capability, produce factors that suppress T-cell proliferation and activity, and are generally better adapted to scavenging debris, promoting angiogenesis, repairing and remodeling wounded/damaged tissues [3]. Recent studies show that TAM cells also play an essential role in inducing invasion and metastasis of breast tumors [4,5]. TAM cells secrets EGF to induce the proliferation and invasion of surrounding tissues by tumor cells [6]. Eventually, migratory cancer cells follow EGF gradient, enter the circulation, and spread throughout the body. Depletion of macrophages effectively blocked metastasis in a mouse model [7]. Thus, disrupt of TAM function will provide a novel approach to develop anti-cancer therapies.Recruitment of macrophages to the proximity of tumors was mediated by CSF-1, a growth factor, secreted by tumor cells [6]. CSF-1 also stimulates the proliferation, differentiation, and survival of macrophages [8]. Macrophages stimulated with CSF-1 show immediate cell polarization, actin reorganization, and migration to the CSF-1 secreting tumor cells [9]. Extensive studies have revealed the molecular mechanism of chemokine receptor, a subfamily of G-protein-coupled receptors, -mediated leukocyte trafficking during inflammation [10,11]. However, the signal transduction pathway that regulates CSF-1-induced macrophage migration is still largely unknown. Investigating molecular mechanism of CSF-1-mediated macrophage chemotaxis will provide new insights to block the formation and accumulation of TAM cells.The Akt/PKB family, Akt1, 2, and 3, plays a critical role in regulating cell growth, proliferation, survival, and metabolism [12,13]. Akt1 and 2 are expressed in most cell types and tissues 894while Akt3 shows a more r...

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Chemokines and chemokine receptors in leukocyte trafficking

Cited by 585 publications

References 184 publications

Regulation of innate immunity by inositol 1,3,4,5-tetrakisphosphate

Regulation of innate immunity by inositol 1,3,4,5-tetrakisphosphate

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

Akt2 is required for macrophage chemotaxis

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Chemokines and chemokine receptors in leukocyte trafficking

Cited by 585 publications

References 184 publications

Regulation of innate immunity by inositol 1,3,4,5-tetrakisphosphate

Regulation of innate immunity by inositol 1,3,4,5-tetrakisphosphate

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

Akt2 is required for macrophage chemotaxis

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