Signal transduction involved in MCP-1–mediated monocytic transendothelial migration

Cambien, Béatrice; Pomeranz, Manuel; Millet, Marie-Ange; Rossi, Bernard; Schmid-Alliana, Annie

doi:10.1182/blood.v97.2.359

Cited by 121 publications

(102 citation statements)

References 55 publications

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“…The majority of studies have used pharmacologic inhibitors to understand possible pathways that may be involved. Some pathways that have been implicated as regulators of monocyte chemotaxis to MCP-1 include phosphatidylinositol 3 kinase, mitogen-activated protein kinases, protein kinase C, and PLA 2 (23,(41)(42)(43). Although studies from knockout mice indicate the importance of phosphatidylinositol 3 kinase in macrophage chemotaxis to a variety of stimuli, chemotaxis to MCP-1 was not evaluated (44).…”

Section: Discussionmentioning

confidence: 99%

Calcium-Independent Phospholipase A2 Is Required for Human Monocyte Chemotaxis to Monocyte Chemoattractant Protein 1

Carnevale

Cathcart

2001

The Journal of Immunology

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Monocyte chemoattractant protein 1 (MCP-1) has an important influence on monocyte migration into sites of inflammation. Our understanding of the signal transduction pathways involved in the response of monocytes to MCP-1 is quite limited yet potentially significant for understanding and manipulating the inflammatory response. Prior studies have demonstrated a crucial regulatory role for cytosolic phospholipase A2 (cPLA2) in monocyte chemotaxis to MCP-1. In these studies we investigated the role for another PLA2, calcium-independent PLA2 (iPLA2) in comparison to cPLA2. Pharmacological inhibitors of PLA2 were found to substantially inhibit chemotaxis. Using antisense oligodeoxyribonucleotide treatment we found that iPLA2 expression is required for monocyte migration to MCP-1. Complete blocking of the chemotactic response was observed with inhibition of either iPLA2 or cPLA2 expression by their respective antisense oligodeoxyribonucleotide. In reconstitution experiments, lysophosphatidic acid completely restored MCP-1-stimulated migration in iPLA2-deficient monocytes, whereas lysophosphatidic acid was without effect in restoring migration in cPLA2-deficient monocytes. To the contrary, arachidonic acid fully restored migration of cPLA2-deficient monocytes while having no effect on the iPLA2-deficient monocytes. Additional studies revealed that neither enzyme appears to be upstream of the other indicating that iPLA2 and cPLA2 represent parallel regulatory pathways. These data demonstrate novel and distinct roles for these two phospholipases in this critical step in inflammation.

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Section: Discussionmentioning

confidence: 99%

Calcium-Independent Phospholipase A2 Is Required for Human Monocyte Chemotaxis to Monocyte Chemoattractant Protein 1

Carnevale

Cathcart

2001

The Journal of Immunology

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“…The next step, leukocytetight adhesion, occurs through the interaction of leukocyte integrins (e.g., lymphocyte function-associated antigen 1 [LFA-1], Mac-1 [CD11b/CD18]) with counterligands on ECs (e.g., intercellular adhesion molecule 1 [ICAM-1]) (29). Finally, transmigration of leukocytes through the endothelium and the vascular wall is mediated by chemokines, such as monocyte chemotactic protein 1 (MCP-1) (30).…”

Section: Statins As Antiinflammatory Drugs: Effects On Cells and Tissuesmentioning

confidence: 99%

Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

Abeles

Pillinger

2006

Arthritis & Rheumatism

135

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“…Chemokine receptors are linked to a number of downstream signal transduction pathways that mediate their biological effects (Bajetto et al, 2002). In immune cells, CCL2 signaling is reported to involve Gi/Go proteins and cellular calcium flux or activation of phospholipase C (Cambien et al, 2001;Dubois et al, 1996;Kuang et al, 1996). CCL2 has also been shown to trigger tyrosine phosphorylation and activation of Janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) pathway in immune cells (Mellado et al, 1998) and to activate mitogen-activated protein kinases (MAPK) (Dubois et al, 1996;Jimenez-Sainz et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

The chemokine CCL2 activates p38 mitogen-activated protein kinase pathway in cultured rat hippocampal cells

Cho

Gruol

2008

Journal of Neuroimmunology

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Emerging evidence indicates that chemokines can regulate both the physiology and biochemistry of CNS neurons and glia. In the current study, Western blot analysis showed that in rat hippocampal neuronal/glial cultures the signal transduction pathway activated by CCL2, a chemokine expressed in the normal brain and at elevated levels during neuroinflammation, involves a G-protein coupled receptor, p38 MAPK as well as its immediate upstream kinase MKK3/6, and the downstream transcription factor CREB. ERK 1/2 and the transcription factors STAT1 and STAT3 do not play a prominent role. CCL2 also altered Ca 2+ influx and synaptic network activity in the hippocampal neurons. These results suggest an important role for p38 MAPK and CREB in hippocampal actions of CCL2.

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Signal transduction involved in MCP-1–mediated monocytic transendothelial migration

Cited by 121 publications

References 55 publications

Calcium-Independent Phospholipase A2 Is Required for Human Monocyte Chemotaxis to Monocyte Chemoattractant Protein 1

Calcium-Independent Phospholipase A2 Is Required for Human Monocyte Chemotaxis to Monocyte Chemoattractant Protein 1

Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

The chemokine CCL2 activates p38 mitogen-activated protein kinase pathway in cultured rat hippocampal cells

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