Distinct regulation of C3a-induced MCP-1/CCL2 and RANTES/CCL5 production in human mast cells by extracellular signal regulated kinase and PI3 kinase

Venkatesha, Rampura T.; Thangam, E. Berla; Zaidi, Asifa K.; Ali, Hydar

doi:10.1016/j.molimm.2004.09.009

Cited by 113 publications

(109 citation statements)

References 40 publications

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“…Finally, in mast cell lines C3a mediates its effects by transient calcium ion mobilization and, in contrast to what has been described for other cells, sustained ERK1/2 and Akt phosphorylation (34). Overall, there is limited information available on the signaling pathways activated by C3aR stimulation.…”

Section: C3a and C5a Are Chemotactic Factors For Human Mesenchymal Stmentioning

confidence: 86%

C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation

Schraufstätter

DiScipio

Zhao

et al. 2009

The Journal of Immunology

164

136

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Mesenchymal stem cells (MSCs) have a great potential for tissue repair, especially if they can be delivered efficiently to sites of tissue injury. Since complement activation occurs whenever there is tissue damage, the effects of the complement activation products C3a and C5a on MSCs were examined. Both C3a and C5a were chemoattractants for human bone marrow-derived MSCs, which expressed both the C3a receptor (C3aR) and the C5a receptor (C5aR; CD88) on the cell surface. Specific C3aR and C5aR inhibitors blocked the chemotactic response, as did pertussis toxin, indicating that the response was mediated by the known anaphylatoxin receptors in a Gi activation-dependent fashion. While C5a causes strong and prolonged activation of various signaling pathways in many different cell types, the response observed with C3a is generally transient and weak. However, we show herein that in MSCs both C3a and C5a caused prolonged and robust ERK1/2 and Akt phosphorylation. Phospho-ERK1/2 was translocated to the nucleus in both C3a and C5a-stimulated MSCs, which was associated with subsequent phosphorylation of the transcription factor Elk, which could not be detected in other cell types stimulated with C3a. More surprisingly, the C3aR itself was translocated to the nucleus in C3a-stimulated MSCs, especially at low cell densities. Since nuclear activation/translocation of G protein-coupled receptors has been shown to induce long-term effects, this novel observation implies that C3a exerts far-reaching consequences on MSC biology. These results suggest that the anaphylatoxins C3a and C5a present in injured tissues contribute to the recruitment of MSCs and regulation of their behavior.

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Section: C3a and C5a Are Chemotactic Factors For Human Mesenchymal Stmentioning

confidence: 86%

C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation

Schraufstätter

DiScipio

Zhao

et al. 2009

The Journal of Immunology

164

136

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“…27, 28) and p38 (29). Furthermore, C3a and C5a increase the activation of phosphatidylinositol 3-kinase, Akt, and mammalian target of rapamycin (30,31), three other proteins strongly associated with neoplasia when overexpressed (32,33). FIGURE 1.…”

Section: Complement Promotes Oncogenesismentioning

confidence: 96%

“…Endothelial cells constitutively express C3aR and activate ERK1/2 following C3a/C3aR binding (27,28). Leukocytes show sustained ERK1/2 and Akt pathway activation in response to C3a (30), whereas macrophages activate MAPK p38 pathways in response to C5a (29). C5a causes potent activation of ERK1/2, Akt, and JNK in monocytes (36), neutrophils (37), and neurons (38), and induces transactivation of epidermal growth factor receptor in endothelial cells, enhancing their migration (27).…”

Section: Complement Promotes Oncogenesismentioning

confidence: 99%

Cancer and the Complement Cascade

Rutkowski

Sughrue

Kane

et al. 2010

Molecular Cancer Research

225

249

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Despite significant research on the role of inflammation and immunosurveillance in the immunologic microenvironment of tumors, little attention has been given to the oncogenic capabilities of the complement cascade. The recent finding that complement may contribute to tumor growth suggests an insidious relationship between complement and cancer, especially in light of evidence that complement facilitates cellular proliferation and regeneration. We address the hypothesis that complement proteins promote carcinogenesis and suggest mechanisms by which complement can drive the fundamental features of cancer. Evidence shows that this diverse family of innate immune proteins facilitates dysregulation of mitogenic signaling pathways, sustained cellular proliferation, angiogenesis, insensitivity to apoptosis, invasion and migration, and escape from immunosurveillance. Given that the traditionally held functions for the complement system include innate immunity and cancer defense, our review suggests a new way of thinking about the role of complement proteins in neoplasia.

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“…In endothelial cells C3aR is connected with pertussis-toxin insensitive Gα16 [70], following activation of protein-kinase C by phospholipase C. In astrocytes the protein (MAP) kinases Erk1 and Erk2 are activated [52,71]. In mast cells C3aR binding by C3a activates cytokine production through a complex intracellular signals involving PI3K, Akt-phosohorylation and MAP kinase Erk1 and ERK2 [72].…”

Section: Anaphylatoxins Receptorsmentioning

confidence: 99%

Anaphylatoxins: From Supposed Toxin Anaphylactics to Effective Mediators of the Early Events of Inflammation

Silva¹

2012

OJVM

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This review updates original data describing the experiments showing the complement origin of anaphylatoxins unexplainable submerged under the surface of the articles related to the subject. Next, recalls subsequent data describing the anaphylatoxins peptide nature and sequences, the cell receptors with which they interact and activate and the outcome of the cell responses. The review continues by highlighting the anaphylatoxin biological properties focusing on the unequivocal participation of these mediators in inflammation. The review concludes bringing data reinforcing the promising use of these peptides as molecular primers to create specific and efficient pharmacological antagonists.

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Distinct regulation of C3a-induced MCP-1/CCL2 and RANTES/CCL5 production in human mast cells by extracellular signal regulated kinase and PI3 kinase

Cited by 113 publications

References 40 publications

C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation

C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation

Cancer and the Complement Cascade

Anaphylatoxins: From Supposed Toxin Anaphylactics to Effective Mediators of the Early Events of Inflammation

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