OBJECTIVETo study the effect of C5-siRNA on pathological changes after myocardial ischemia in rats.

METHODSThirty healthy Sprague-Dawley rats were randomly divided into sham-operated group, ischemia group and C5-siRNA group. The cardiac ischemia models were established in ischemia group and C5-siRNA group by ligating the proximal end of the left anterior descending (LAD) coronary artery. The rats were infused with 100 microl/kg of C5-siRNA into myocardial tissue in C5-siRNA group and equal amount of normal saline in ischemia group and sham-operated group after ligating the LAD coronary artery for 30 min and then performed of ischemia for 4 hours. The cardiac index and left ventricular mass index were determined, morphological changes of myocardial tissue observed under optical microscope and the expression of C5 was detected by immunohistochemical staining and image analysis system.

RESULTSThere were no statistically significant difference between the three groups in the left ventricular mass index and cardiac index in the rats after ischemia for 4 hours. Light microscopy indicated edema and degeneration of the myocardial tissue were milder in C5-siRNA group than in ischemia group, a small amount of red blood cells existed in the myocardial stroma of the former. The expression of C5 was increased more significantly in ischemia group and C5-siRNA group than in sham-operated group (P<0.001), but was decreased in C5-siRNA group more than in ischemia group with no statistically significant difference between the two groups (P=0.132).

CONCLUSIONC5-siRNA could attenuate myocardial ischemia injury in rats by reducing inflammatory cell infiltration and expression of C5.

Animals ; Complement C5 ; genetics ; Male ; Myocardial Ischemia ; genetics ; pathology ; Myocardial Reperfusion Injury ; prevention & control ; RNA Interference ; RNA, Small Interfering ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, Anaphylatoxin C5a ; genetics

Through the applications of high-sensitivity flow cytometry of FLAER and the treatment of eculizumab, it is necessary to understand of paroxysmal nocturnal hemoglobinuria (PNH) from a new point of view. The results of studies demonstrate that treatment with eculizumab alters the natural history of PNH by virtually eradicating thromboembolic complications, inhibiting of intravascular hemolysis and reducing or eliminating transfusion requirements. Eculizumab treatment may also reduce disease-related mortality. This review focuses on the studies to define the relationship between PNH and bone marrow failure syndromes and to characterize the long-term outcome of patients with PNH treated with eculizumab. New therapeutic strategies aimed at controlling extravascular and intravascular hemolysis are discussed.
Antibodies, Monoclonal, Humanized ; therapeutic use ; Complement C5 ; immunology ; Hemoglobinuria, Paroxysmal ; diagnosis ; therapy ; Humans ; Prognosis

C3 glomerulopathy (C3G) is a recently defined pathological entity characterized by C3 accumulation with absent or scant immunoglobulin deposition, leading to variable glomerular inflammation. The clinical presentation of patients with C3G is highly variable, as they may present with symptoms ranging from microscopic or mild proteinuria to full-blown nephrotic syndrome, with or without renal impairment. However, there is no consensus recommendation for specific treatment in children with C3G. Recently, new therapies have been suggested to target complement pathways, owing to an improvement in the understanding of the pathogenesis of C3G. C3G complement blockade with eculizumab, a monoclonal antibody targeted against complement C5, inhibits activation of the alternative complement pathway. We could not use eculizumab owing to its high price; thus, we administered oral prednisolone and mycophenolate mofetil (MMF). MMF was replaced with cyclosporine because proteinuria persisted, with a consistently low serum C3 level; we tapered off the prednisolone because of a Cushingoid appearance and amenorrhea. Thereafter, proteinuria improved, and the serum C3 level returned to normal. Thus, we report the effectiveness of cyclosporine in a patient with C3G and an inadequate response to prednisolone and MMF, who was detected via school urinary screening.
Amenorrhea ; Child* ; Complement C5 ; Complement Pathway, Alternative ; Complement System Proteins ; Consensus ; Cyclosporine* ; Female* ; Humans ; Immunoglobulins ; Inflammation ; Mass Screening ; Nephrotic Syndrome ; Prednisolone ; Proteinuria

In order to explore the specificity of complement C5 in the postmortem diagnosis of myocardial infarction, changes of C5 staining in normal, infarcted and other non-infarcted myocardia with direct or indirect myocardial injuries (myocarditis, mechanical asphyxia, electrocution, hemorrhagic shock, cardiac contusion and organophosphate poisoning) were studied with immunohistochemistry and image analysis. The results showed that positive C5 staining could be observed in groups of myocardial infarction and myocarditis, but not in groups of mechanical asphyxia, electrocution, hemorrhagic shock, cardiac contusion, and organophosphate poisoning. It is indicated that positive reaction of C5 could only be affected by myocarditis, which means that it was more specific for the diagnosis of myocardial infarction.
Adolescent ; Adult ; Complement C5/analysis* ; Female ; Forensic Medicine ; Humans ; Male ; Myocardial Infarction/diagnosis* ; Myocardium/chemistry* ; Sensitivity and Specificity

BACKGROUND: Decay accelerating factor (DAF/CD55), regulates the complement system by accelerating decay of the C3 convertase, has been described in several malignancies, however, the clinicopathologic significance of CD55 and its receptor CD97 has not been fully investigated. We examined the expression patterns of both CD55 and CD97 and their association with clinicopathologic parameters in colorectal cancers (CRCs). METHODS: Expression patterns of CD55 and CD97 in the stroma and tumor cells at tumor center and invasive front were examined in 130 CRCs, and their significance was statistically evaluated. RESULTS: CD55-high stroma was correlated with tumor border (p=0.006) and invasion depth (p=0.013). CD55-high tumor cells at tumor center and invasive front were correlated with histologic grade, and CD55-high tumor cells at invasive front with tumor, node and metastasis (TNM) stage (p<0.05). CD97-high stroma was correlated with lymph node metastasis (p=0.016) and TNM stage (p=0.030). CD97-high tumor cells at tumor center and invasive front were correlated with tumor size and CD97-high tumor cells at tumor center with tumor border (p<0.05). Patients with CD55-high stroma showed poor overall and recurrence-free survival (p<0.05) in univariate analysis, and were independently associated with short recurrence-free survival (p=0.025) in multivariate analysis. CONCLUSIONS: Stromal CD55 overexpression would be an indicator of adverse clinical outcome and a useful prognostic factor.
Antigens, CD55 ; Calcium Hydroxide ; Colorectal Neoplasms ; Complement C3-C5 Convertases ; Complement System Proteins ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Zinc Oxide

Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome characterized by micro-angiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The major pathogenesis of aHUS involves dysregulation of the complement system. Eculizumab, which blocks complement C5 activation, has recently been proven as an effective agent. Delayed diagnosis and treatment of aHUS can cause death or end-stage renal disease. Therefore, a diagnosis that differentiates aHUS from other forms of thrombotic microangiopathy is very important for appropriate management. These guidelines aim to offer recommendations for the diagnosis and treatment of patients with aHUS in Korea. The guidelines have largely been adopted from the current guidelines due to the lack of evidence concerning the Korean population.
Acute Kidney Injury ; Anemia, Hemolytic ; Atypical Hemolytic Uremic Syndrome* ; Complement C5 ; Complement System Proteins ; Delayed Diagnosis ; Diagnosis ; Humans ; Kidney Failure, Chronic ; Korea* ; Thrombocytopenia ; Thrombotic Microangiopathies

Therapeutic dentin regeneration remains difficult to achieve, and a majority of the attention has been given to anabolic strategies to promote dentinogenesis directly, whereas, the available literature is insufficient to understand the role of inflammation and inflammatory complement system on dentinogenesis. The aim of this study is to determine the role of complement C5a receptor (C5aR) in regulating dental pulp stem cells (DPSCs) differentiation and in vivo dentin regeneration. Human DPSCs were subjected to odontogenic differentiation in osteogenic media treated with the C5aR agonist and C5aR antagonist. In vivo dentin formation was evaluated using the dentin injury/pulp-capping model of the C5a-deficient and wild-type mice. In vitro results demonstrate that C5aR inhibition caused a substantial reduction in odontogenic DPSCs differentiation markers such as DMP-1 and DSPP, while the C5aR activation increased these key odontogenic genes compared to control. A reparative dentin formation using the C5a-deficient mice shows that dentin regeneration is significantly reduced in the C5a-deficient mice. These data suggest a positive role of C5aR in the odontogenic DPSCs differentiation and tertiary/reparative dentin formation. This study addresses a novel regulatory pathway and a therapeutic approach for improving the efficiency of dentin regeneration in affected teeth.
Animals ; Cell Differentiation/physiology* ; Cells, Cultured ; Complement C5a/metabolism* ; Dental Pulp/physiology* ; Dentin ; Mice ; Receptor, Anaphylatoxin C5a ; Stem Cells

In the intestinal mucosal surface, microfold cells (M cells) are the representative gateway for the uptake of luminal antigens. At the same time, M cells are the primary infection site for pathogens invading mucosal surface for their infection. Although it is well recognized that many mucosal pathogens exploit the M cells for their infection, the mechanism to infect M cells utilized by pathogens is not clearly understood yet. In this study, we found that M cells expressing complement 5a (C5a) receptor (C5aR) also express Toll-like receptor (TLR) 1/2 and TLR4. Infection of Yersinia enterocolitica, an M cell-invading pathogen, synergistically regulated cyclic adenosine monophosphate-dependent protein kinase A (cAMP-PKA) signaling which are involved in signal crosstalk between C5aR and TLRs. In addition, Y. enterocolitica infection into M cells was enhanced by C5a treatment and this enhancement was abrogated by C5a antagonist treatment. Finally, Y. enterocolitica infection into M cells was unsuccessful in C5aR knock-out mice. Collectively, we suggest that exploit the crosstalk between C5aR and TLR signaling is one of infection mechanisms utilized by mucosal pathogens to infect M cells.
Adenosine ; Animals ; Complement C5a* ; Complement System Proteins* ; Cyclic AMP-Dependent Protein Kinases ; Mice ; Mice, Knockout ; Phenobarbital ; Receptor, Anaphylatoxin C5a* ; Toll-Like Receptors* ; Yersinia enterocolitica* ; Yersinia*

A 28-year-old man with a history of alcohol abuse was diagnosed with acute pancreatitis based on clinical symptoms, laboratory findings and computed tomography findings. On the second day of hospitalization, he complained of sudden visual disturbance. The ophthalmologic examination showed Purtscher's-like retinopathy. Two weeks after initial presentation, his vision was significantly improved along with epigastric pain. Retinal arteriolar occlusion by complement-mediated leukoembolization is the proposed pathogenic mechanism of Purtscher's-like retinopathy. Increased activity of proteases such as trypsin, associated with acute pancreatitis might be linked with the production of complement C5a. We report a rare case of Purtscher's-like retinopathy associated with acute pancreatitis.
Adult ; Alcoholism ; Complement C5a ; Hospitalization ; Humans ; Pancreatitis* ; Peptide Hydrolases ; Retinaldehyde ; Trypsin

Role of Ca2+/calmodulin complex in intracellular Ca2+ mobilization in neutrophils has not been clearly elucidated. In this study, effects of chlorpromazine, trifluoperazine and imipramine on the intracellular Ca2+ mobilization, including Ca2+ influx, in C5a-activated neutrophils were investigated. Complement C5a-stimulated superoxide production and myeloperoxidase release in neutrophils were inhibited by chlorpromazine, trifluoperazine and imipramine, except no effect of imipramine on myeloperoxidase release. A C5a-elicited elevation of (Ca2+)i in neutrophils was inhibited by chlorpromazine, trifluoperazine, imipramine, staurosporine, genistein, EGTA, and verapamil but not affected by pertussin toxin. The intracellular Ca2+ release in C5a-activated neutrophils was not affected by chlorpromazine and imipramine. Chlorpromazine and imipramine inhibited Mn2+ influx by C5a-activated neutrophils. Thapsigargin-evoked Ca2+ entry was inhibited by chlorpromazine, trifluoperazine, imipramine, genistein, EGTA and verapamil, while in the activation process of neutrophils. The depressive action of calmodulin inhibitors on the elevation of cytosolic Ca2+ level in C5a-activated neutrophils appears to be accomplished by inhibition of Ca2+ influx from the extracellular medium.
Calmodulin* ; Chlorpromazine ; Complement C5a ; Complement System Proteins* ; Cytosol ; Depression* ; Egtazic Acid ; Genistein ; Imipramine ; Neutrophils* ; Peroxidase ; Staurosporine ; Superoxides ; Trifluoperazine ; Verapamil