Mast cell activation is characterized by upregulation of a functional anaphylatoxin C5a receptor

Soruri, Afsaneh; Grigat, Jasmin; Kiafard, Ziba; Zwirner, Jörg

doi:10.1186/1471-2172-9-29

Cited by 22 publications

(16 citation statements)

References 37 publications

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“…It also induces degranulation in purified human skin mast cells, peripheral blood CD34 + cell-derived mast cells and a newly developed human mast cell line, LAD2 cells (Fukuoka et al, 2008; Lappalainen et al, 2007; Oskeritzian et al, 2005; Venkatesha et al, 2005; Woolhiser et al, 2004). By contrast, C3a does not induce degranulation in murine peritoneal mast cells, bone marrow-derived mast cells or rat basophilic leukemia, RBL-2H3 cells (Erdei et al, 2004; Soruri et al, 2008). C3a, however, causes substantial degranulation in rat peritoneal mast cells via a pathway that appears to be independent of cell surface C3a receptors (Fukuoka and Hugli, 1990; Mousli et al, 1992).…”

Section: Introductionmentioning

confidence: 81%

“…An important feature of Mrg receptors that distinguishes them from the C3a receptor is that they are low affinity receptors and require ligand in the micromolar range to induce full biological responses (Fukuoka et al, 2008; Robas et al, 2003; Tatemoto et al, 2006). It is noteworthy that rat and mouse peritoneal mast cells do not express the C3a receptor (Mousli et al, 1992; 1994; Soruri et al, 2008) but C3a causes degranulation in rat peritoneal mast cells with an EC 50 value of ~1 µM (Mousli et al, 1992), which is in contrast to the EC 50 value of ~3 nM in human mast cells (Fig. 1).…”

Section: Discussionmentioning

confidence: 99%

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G protein coupled receptor specificity for C3a and compound 48/80-induced degranulation in human mast cells: Roles of Mas-related genes MrgX1 and MrgX2

Kashem

Subramanian

Collington

et al. 2011

European Journal of Pharmacology

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Although human mast cells express G protein coupled receptors for the anaphylatoxin C3a, previous studies indicated that C3a causes mast cell degranulation, at least in part, via a C3a receptor-independent mechanism similar to that proposed for polycationic molecules such as compound 48/80. The purpose of the present study was to delineate the receptor specificity of C3a-induced degranulation in human mast cells. We found that C3a, a C3a receptor “superagonist” (E7) and compound 48/80 induced Ca2+ mobilization and degranulation in a differentiated human mast cell line, LAD2. However, C3a and E7 caused Ca2+ mobilization in an immature mast cell line, HMC-1 but compound 48/80 did not. We have previously shown that LAD2 cells express MrgX1 and MrgX2 but HMC-1 cells do not. To delineate the receptor specificity for C3a and compound 48/80 further, we generated stable transfectants expressing MrgX1 and MrgX2 in a rodent mast cell line, RBL-2H3 cells. We found that compound 48/80 caused degranulation in RBL-2H3 cells expressing MrgX1 and MrgX2 but C3a did not. By contrast, E7 activated RBL-2H3 cells expressing MrgX2 but not MrgX1. These findings demonstrate that in contrast to previous reports, C3a and compound 48/80 do not use a shared mechanism for mast cell degranulation. It shows that while compound 48/80 utilizes MrgX1 and MrgX2 for mast cell degranulation C3a does not. It further reveals the novel finding that the previously characterized synthetic peptide, C3a receptor “superagonist” E7 activates human mast cells via two mechanisms; one involving the C3a receptor and the other MrgX2.

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Section: Introductionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

G protein coupled receptor specificity for C3a and compound 48/80-induced degranulation in human mast cells: Roles of Mas-related genes MrgX1 and MrgX2

Kashem

Subramanian

Collington

et al. 2011

European Journal of Pharmacology

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“…Within this context, much attention has been directed to therapeutic strategies aimed at inhibiting neurotoxic glial cell activation [135]. [124,125] (b) N-Palmitoylethanolamine: a wide-acting anti-inflammatory and neuroprotective N-acylethanolamine In addition to synthetic chemistry efforts aimed at controlling neuroinflammation, we now recognize the existence of endogenous molecules involved in endogenous protective mechanisms that are activated in the body as a result of different types of tissue damage or stimulation of inflammatory responses and nociceptive fibres. One interesting group of such molecules are the N-acylethanolamines, a class of naturally occurring lipidic mediator molecules composed of a fatty acid and ethanolamine, namely the fatty acid ethanolamines (FAEs).…”

Section: Microglia and Mast Cells As Therapeutic Targetsmentioning

confidence: 99%

Mast cell–glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide

Skaper

Facci

2012

Phil. Trans. R. Soc. B

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Communication between the immune and nervous systems depends a great deal on pro-inflammatory cytokines. Both astroglia and microglia, in particular, constitute an important source of inflammatory mediators and may have fundamental roles in central nervous system (CNS) disorders from neuropathic pain and epilepsy to neurodegenerative diseases. Glial cells respond also to pro-inflammatory signals released from cells of immune origin. In this context, mast cells are of particular relevance. These immune-related cells, while resident in the CNS, are able to cross a compromised bloodspinal cord and blood-brain barrier in cases of CNS pathology. Emerging evidence suggests the possibility of mast cell-glia communication, and opens exciting new perspectives for designing therapies to target neuroinflammation by differentially modulating the activation of non-neuronal cells normally controlling neuronal sensitization-both peripherally and centrally. This review aims to provide an overview of recent progress relating to the pathobiology of neuroinflammation, the role of glia, neuro-immune interactions involving mast cells and the possibility that glia-mast cell interactions contribute to exacerbation of acute symptoms of chronic neurodegenerative disease and accelerated disease progression, as well as promotion of pain transmission pathways. Using this background as a starting point for discussion, we will consider the therapeutic potential of naturally occurring fatty acid ethanolamides, such as palmitoylethanolamide in treating systemic inflammation or blockade of signalling pathways from the periphery to the brain in such settings.

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“…These include cells of myeloid origin (22), non-myeloid origin (23), dendritic cells (24), monocyte/macrophages (25), and neutrophils (26). Resting mast cells express C5aR below threshold levels, but stimulation with phorbol myristate acetate (PMA) or ionomycin results in increases in C5aR expression as well as in slight increases in C3aR receptors (27). …”

Section: Introductionmentioning

confidence: 99%

Role of C3a Receptors, C5a Receptors, and Complement Protein C6 Deficiency in Collagen Antibody-Induced Arthritis in Mice

Banda

Hyatt

Antonioli

et al. 2012

The Journal of Immunology

118

101

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The complement system, especially the alternative pathway (AP), plays essential roles in the induction of injury in collagen antibody-induced arthritis (CAIA) in mice. The goal of the current study was to directly compare the roles of receptors for C3a and C5a, as well as the membrane attack complex (MAC), as effector mechanisms in the pathogenesis of CAIA. Clinical disease activity (CDA) in C3aR−/−, C5aR−/−, and C6 deficient (C6-def) mice was decreased by 52%, 94%, and 65%, respectively, as compared with WT mice. Decreases in histopathologic injury as well as in IgG and C3 deposition paralleled the CDA. A decrease in the percentage of synovial neutrophils was observed in C3aR−/−, C5aR−/−, and C6-def mice, and a decrease in macrophages was observed in C3aR−/− and C5aR−/−, but not in C6-def, mice. Synovial mRNA obtained by laser capture microdissection exhibited a decrease in TNF-α in C5aR−/− mice and in IL-1β in both C5aR−/− and C6-def mice, while C3aR−/− mice demonstrated no change in either cytokine. Our findings show that absent C3aR-, C5aR- or MAC-initiated effector mechanisms each decreases susceptibility to CAIA, with clinical effects most pronounced in C5aR deficient mice. Although the absence of C3aR, C5aR, or C6 led to differential deficiencies in effector mechanisms, decreased proximal joint IgG and C3 deposition was common to all three genotypes in comparison to WT mice. These data suggest the existence of positive feedback amplification pathways downstream of all three effectors that promote additional IgG deposition and C3 activation in the joint.

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Mast cell activation is characterized by upregulation of a functional anaphylatoxin C5a receptor

Abstract: Background: Mast cells (MC) are key effector cells of allergic diseases and resistance to helminthic parasites and induce or amplify diverse innate and adaptive immune responses. The signals controlling MC mobilization during inflammation are not fully understood.

Cited by 22 publications

References 37 publications

G protein coupled receptor specificity for C3a and compound 48/80-induced degranulation in human mast cells: Roles of Mas-related genes MrgX1 and MrgX2

G protein coupled receptor specificity for C3a and compound 48/80-induced degranulation in human mast cells: Roles of Mas-related genes MrgX1 and MrgX2

Mast cell–glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide

Role of C3a Receptors, C5a Receptors, and Complement Protein C6 Deficiency in Collagen Antibody-Induced Arthritis in Mice

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