Expression of Receptors for Complement Anaphylatoxins C3a and C5a Following Permanent Focal Cerebral Ischemia in the Mouse

Beek, Johan van; Bernaudin, Myriam; Petit, Edwige; Gasque, Philippe; Nouvelot, A.; MacKenzie, Eric T.; Fontaine, Marc

doi:10.1006/exnr.1999.7273

Cited by 144 publications

(133 citation statements)

References 44 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…Up to now the presence of C3aR and C5aR has been documented in the adult rodent brain, where the two receptors are expressed by glial cells, astrocyte (11)(12)(13), and microglia (14,15). C3aR and C5aR are present both in vitro (11)(12)(13)(14) and in vivo (15) and are upregulated in these cells after inflammation (15)(16)(17). In situ hybridization and immunohistochemistry analysis also revealed a constitutive expression of mouse and rat C3aR in cortical and hippocampal neurons (17,19) as well as in cerebellar Purkinje cells (19).…”

Section: Discussionmentioning

confidence: 99%

“…C3aR and C5aR are expressed in myeloid cells (4 -8) and, more surprisingly, in non-myeloid cells and tissues (7)(8)(9)(10). In the central nervous system it has been shown that C3aR and C5aR are constitutively expressed by glial cells in vitro (11)(12)(13)(14) and in vivo (15) and that the expression of C3aR and C5aR is increased in inflammatory conditions (15)(16)(17).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of C3a and C5a Receptors in Rat Cerebellar Granule Neurons during Maturation

Bénard

Gonzalez

Schouft

et al. 2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

There is now clear evidence that the Complement anaphylatoxin C3a and C5a receptors (C3aR and C5aR) are expressed in glial cells, notably in astrocytes and microglia. In contrast, very few data are available concerning the possible expression of these receptors in neurons. Here, we show that transient expression of C3aR and C5aR occurs in cerebellar granule neurons in vivo with a maximal density in 12-day-old rat, suggesting a role of these receptors during development of the cerebellum. Expression of C3aR and C5aR mRNAs and proteins was also observed in vitro in cultured cerebellar granule cells. Quantification of the mRNAs by real-time reverse transcription-PCR showed a peak of expression at day 2 in vitro (DIV 2); the C3aR and C5aR proteins were detected by Western blot analysis at DIV 4 and by flow cytometry and immunocytochemistry in differentiating neurons with a maximum density at DIV 4 -9. Apoptosis of granule cells plays a crucial role for the harmonious development of the cerebellar cortex. We found that, in cultured granule neurons in which apoptosis was induced by serum deprivation and low potassium concentration, a C5aR agonist promoted cell survival and inhibited caspase-3 activation and DNA fragmentation. The neuroprotective effect of the C5aR agonist was associated with a marked inhibition of caspase-9 activity and partial restoration of mitochondrial integrity. Our results provide the first evidence that C3aR and C5aR are both expressed in cerebellar granule cells during development and that C5a, but not C3a, is a potent inhibitor of apoptotic cell death in cultured granule neurons.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Characterization of C3a and C5a Receptors in Rat Cerebellar Granule Neurons during Maturation

Bénard

Gonzalez

Schouft

et al. 2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…C5aR is widely expressed on various cells in central nervous system 17 and involved in many physiological and pathological processes. The C5a-C5aR signal pathway has been proved to participate in many central nervous system diseases, including infection, 25 hypoxic ischemia disease 26 and neurodegeneration. 27 PMX53 is a specific C5aR antagonist with a molecular formula as AcF-[OP(D-Cha)WR].…”

Section: Dissussionmentioning

confidence: 99%

PMX53 protects spinal cord from ischemia-reperfusion injury in rats in the short term

et al. 2015

View full text Add to dashboard Cite

Study design: Experimental study. Objectives: To investigate the effect of pre-treatment with PMX53, a C5aR antagonist, on spinal cord ischemia-reperfusion injury (IRI) in rat. Setting: Department of Neurosurgery, Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi Province, China. Methods: IRI was induced in the lumbar spinal cord by applying a mini aneurysm clamp to the abdominal aorta for 60 min in adult Sprague-Dawley rats. PMX53 (1 mg kg − 1 ) was administered through femoral vein injection 30 min before ischemia on the rats in the PMX53 group (n = 18). The saline group (n = 18) was given saline at the same volume through femoral vein injection. The neurologic outcome of the posterior limbs was assessed by the Basso-Beattie-Bresnahan (BBB) score at 1, 6, 12, 24 and 48 h after reperfusion. Histologic changes of the spinal cord were detected with hematoxylin-eosin (H-E) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect myeloperoxidase (MPO) activity in the spinal cord. Immunohistochemistry was used to investigate the quantity of activated astrocytes and microglia. Results: After pre-treatment with PMX53, neurologic function improved gradually after 6, 12, 24 and 48 h reperfusion. The BBB score of the PMX53 group increased significantly (Po0.05) compared with the saline group. H-E staining showed that pathologic damage in the PMX53 group was reduced. Moreover, administration of PMX53 significantly inhibited neutrophil infiltration in the spinal cord. Levels of MPO activity in the spinal cord were remarkably lower in the PMX53 group (Po0.05). There were also more activated microglia and astrocytes in the spinal cord of the PMX53 group than in the saline group (Po0.05). INTRODUCTIONSpinal cord ischemia-reperfusion injury (SIRI) mainly occurs after operations on the descending thoracic or thoracoabdominal aorta, such as thoracoabdominal aneurysm. 1 SIRI causes various complications, including paraparesis and paraplegia. 2 These complications have been attributed to temporary or permanent ischemia of the spinal cord caused by interruption of the blood supply during aortic cross-clamping. The incidence of paraplegia has been correlated with dissection, rupture and prolonged clamp times. 3 Systemic hypothermia, spinal fluid drainage and preconditioning ischemia were considered to prevent paraplegia, 4 but the effect was limited. Recent studies indicated that pathophysiological mechanisms underlying SIRI are complicated, including the release of inflammatory factors, 5 calcium overload, 6 oxidative stress, 7 excitotoxicity 8 and neuronal apoptosis. 9,10 In addition, there are more mechanisms that remain unclear. It has been found that the inflammatory cascade is activated due to SIRI, including neutrophil and neuroglia mobilization and infiltration, as well as elevated levels of inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6. 11 The complement system, a major component of the innate immune system, is

show abstract

“…C3aR-positive bone marrow-derived cells that participate in host immune responses include mast cells, eosinophils, basophils, neutrophils, dendritic cells (DCs), macrophages, T cells, and B cells (3)(4)(5)(6). The C3aR is also expressed in nonmyeloid tissues, including kidney, brain, lung, heart, and liver (7)(8)(9)(10).…”

mentioning

confidence: 99%

Induction of C3 and CCL2 by C3a in Keratinocytes: A Novel Autocrine Amplification Loop of Inflammatory Skin Reactions

Purwar

Wittmann

Zwirner

et al. 2006

The Journal of Immunology

View full text Add to dashboard Cite

The complement fragment-3a (C3a) acts via a G protein-coupled C3aR and is of importance in allergic and inflammatory diseases. Recent studies suggest the presence of complement proteins in the epidermal compartment and synthesis of some of these proteins (C3, factor B, and factor H) by human primary keratinocytes (KCs) during inflammation. However, expression of C3aR and its role in human KCs is not elucidated thus far. In this study, we demonstrate the expression of C3aR on KCs as detected by quantitative real-time RT-PCR and flow cytometry. IFN-γ and IFN-α strongly up-regulated the surface expression of C3aR on KCs among all other cytokines tested. After up-regulation of C3aR by IFN-γ and IFN-α, we observed the induction of five genes (CCL2, CCL5, CXCL8, CXCL10, and C3) after stimulation of KCs with C3a in microarray analysis. We confirmed the induction of C3 and CCL2 at RNA and protein levels. Furthermore, incubation of C3 with skin mast cells tryptase resulted in the generation of C3 fragments with C3a activity. In conclusion, our data illustrate that epidermal KCs express functional C3aR. The increases of C3 and CCL2 synthesis by C3a and C3 activation by skin mast cell tryptase delineates a novel amplification loop of complement activation and inflammatory responses that may influence the pathogenesis of allergic/inflammatory skin diseases.

show abstract

Expression of Receptors for Complement Anaphylatoxins C3a and C5a Following Permanent Focal Cerebral Ischemia in the Mouse

Cited by 144 publications

References 44 publications

Characterization of C3a and C5a Receptors in Rat Cerebellar Granule Neurons during Maturation

Characterization of C3a and C5a Receptors in Rat Cerebellar Granule Neurons during Maturation

PMX53 protects spinal cord from ischemia-reperfusion injury in rats in the short term

Induction of C3 and CCL2 by C3a in Keratinocytes: A Novel Autocrine Amplification Loop of Inflammatory Skin Reactions

Contact Info

Product

Resources

About