The Intracellular Signaling Pathways Involved in MCP-1-Stimulated T Cell Migration across Microvascular Endothelium

Cai, Jianping; Hudson, Stephen J.; Ye, Min-Wei; Chin, Yee‐Hon

doi:10.1006/cimm.1996.0035

Cited by 34 publications

(20 citation statements)

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“…The EC 50 for Ca 2ϩ flux in the Jurkat CCR2B transfectants ranged from approximately 10 -40 nM depending on the level of surface receptor expression, whereas an EC 50 of about 3.4 nM was obtained for Ca 2ϩ flux in CCR2B HEK-293 transfectants that express high levels of CCR2B (17). Peripheral blood monocytes mobilize Ca 2ϩ in response to low nanomolar concentrations of MCP-1 (27)(28)(29), whereas concentrations as high as 10 nM MCP-1 did not mobilize Ca 2ϩ in normal T cells from peripheral blood (27). Therefore, receptor number as well as differences in the receptor coupling between cell types may contribute to differences in functional activity between peripheral T cells and monocytes as well as between CCR2 expressed in Jurkat and HEK-293 cells.…”

Section: Discussionmentioning

confidence: 96%

Functional Differences Between Monocyte Chemotactic Protein-1 Receptor A and Monocyte Chemotactic Protein-1 Receptor B Expressed in a Jurkat T Cell

Sanders

Crean

Boxer

et al. 2000

The Journal of Immunology

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The monocyte chemotactic protein-1 (MCP-1) receptor (MCP-1R) is expressed on monocytes, a subpopulation of memory T lymphocytes, and basophils. Two alternatively spliced forms of MCP-1R, CCR2A and CCR2B, exist and differ only in their carboxyl-terminal tails. To determine whether CCR2A and CCR2B receptors function similarly, Jurkat T cells were stably transfected with plasmids encoding the human CCR2A or CCR2B gene. Nanomolar concentrations of MCP-1 induced chemotaxis in the CCR2B transfectants that express high, intermediate, and low levels of MCP-1R. Peak chemotactic activity was shifted to the right as receptor number decreased. Five-fold more MCP-1 was required to initiate chemotaxis of the CCR2A low transfectant, but the peak of chemotaxis was similar for the CCR2A and CCR2B transfectants expressing similar numbers of receptors. MCP-1-induced chemotaxis was sensitive to pertussis toxin, implying that both CCR2A and CCR2B are Giα protein coupled. MCP-1 induced a transient Ca2+ flux in the CCR2B transfectant that was partially sensitive to pertussis toxin. In contrast, MCP-1 did not induce Ca2+ flux in the CCR2A transfectant. Since MCP-1 can stimulate chemotaxis of the CCR2A transfectant without inducing Ca2+ mobilization, Ca2+ flux may not be required for MCP-1-induced chemotaxis in the Jurkat transfectants. These results indicate that functional differences exist between the CCR2A and CCR2B transfectants that can be attributed solely to differences in the carboxyl-terminal tail.

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Section: Discussionmentioning

confidence: 96%

Functional Differences Between Monocyte Chemotactic Protein-1 Receptor A and Monocyte Chemotactic Protein-1 Receptor B Expressed in a Jurkat T Cell

Sanders

Crean

Boxer

et al. 2000

The Journal of Immunology

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“…The inhibition of PKC reduces MCP-1-dependent proliferation and IL-6 release. PKC has also been shown to be important for MCP-1 signaling in monocytes and T cells, 29,30 indicating a central role for this pathway in MCP-1 signal transduction.…”

Section: Discussionmentioning

confidence: 99%

Monocyte Chemoattractant Protein-1 Induces Proliferation and Interleukin-6 Production in Human Smooth Muscle Cells by Differential Activation of Nuclear Factor-κB and Activator Protein-1

Viedt

Vogel

Athanasiou

et al. 2002

ATVB

177

124

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Abstract-Inflammatory response and chemotaxis of vascular wall cells play an important pathogenic role in the development of atherosclerosis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant for monocytes. Besides the induction of monocyte recruitment, it has been suggested that MCP-1 may directly activate smooth muscle cells. We investigated whether MCP-1 affects the proliferation and cytokine production of human vascular smooth muscle cells (VSMCs) and determined the underlying signal transduction pathways. Stimulation of VSMCs with MCP-1 induced proliferation and resulted in a concentration-and time-dependent release of the proinflammatory cytokine interleukin-6 (IL-6). Pretreatment with pertussis toxin, GF109203X, and pyrrolidine dithiocarbamate inhibited MCP-1-dependent IL-6 release, suggesting the involvement of G i proteins, protein kinase C, and nuclear factor-B (NF-B). MCP-1 also induced extracellular signal-regulated kinase, which, along with IL-6 release, was inhibited by pertussis toxin. Key Words: atherosclerosis Ⅲ monocyte chemoattractant protein-1 Ⅲ interleukin-6 Ⅲ nuclear factor-B Ⅲ activator protein-1

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“…The estimated function of chemokines in arthritis development is the regulation of inflammation including infiltration of lymphocytes, monocytes, and neutrophils, among others (22)(23)(24)(25). The effectiveness of anti-MIP-1␣, MIP-2, and MCP-1 treatments on arthritis development has been reported in some arthritis models (26,27), but their exact contributions have not been fully elucidated.…”

Section: The Importance Of Il-1␤ and Tnf-␣ And The Noninvolvement Ofmentioning

confidence: 99%

The Importance of IL-1β and TNF-α, and the Noninvolvement of IL-6, in the Development of Monoclonal Antibody-Induced Arthritis

Kagari¹,

Doi²,

Shimozato³

2002

The Journal of Immunology

199

190

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Injection of anti-type II collagen Ab and LPS induces arthritis in mice. The levels of IL-1β, IL-6, and chemokines (macrophage inflammatory protein (MIP)-1α, MIP-2, and monocyte chemoattractant protein-1) in the hind paws increased with the onset of arthritis and correlated highly with arthritis scores. The level of TNF-α was also elevated, but only transiently. Quantitative real-time PCR analysis revealed increases in cytokine and chemokine mRNA. To elucidate the contribution of inflammatory cytokines and chemokines in arthritis development more directly, recombinant proteins, neutralizing Abs, and knockout mice were used. The injection of rIL-1β or TNF-α, but not IL-6 or chemokines, induced arthritis when mice were i.v. preinjected with anti-type II collagen Ab. However, a single injection of recombinant cytokines or chemokines into the hind paws did not induce swelling. Arthritis development was inhibited by neutralizing Ab against IL-1β, TNF-α, or MIP-1α. In contrast, the inhibitory effect by anti-MIP-2 Ab was partial and, surprisingly, Abs to IL-6 and monocyte chemoattractant protein-1 showed no inhibitory effect. Furthermore, arthritis development in IL-1R−/− mice and TNFR−/− mice was not observed at all, but severe arthritis was developed in IL-6−/− mice. These results suggest that IL-1β and TNF-α play more crucial roles than IL-6 or chemokines in this model. Because arthritis was also developed in SCID mice, the development of arthritis in the Ab-induced mice model is due to a mechanism that does not involve T or B cells.

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The Intracellular Signaling Pathways Involved in MCP-1-Stimulated T Cell Migration across Microvascular Endothelium

Cited by 34 publications

References 0 publications

Functional Differences Between Monocyte Chemotactic Protein-1 Receptor A and Monocyte Chemotactic Protein-1 Receptor B Expressed in a Jurkat T Cell

Functional Differences Between Monocyte Chemotactic Protein-1 Receptor A and Monocyte Chemotactic Protein-1 Receptor B Expressed in a Jurkat T Cell

Monocyte Chemoattractant Protein-1 Induces Proliferation and Interleukin-6 Production in Human Smooth Muscle Cells by Differential Activation of Nuclear Factor-κB and Activator Protein-1

The Importance of IL-1β and TNF-α, and the Noninvolvement of IL-6, in the Development of Monoclonal Antibody-Induced Arthritis

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