This study aims to investigate the mechanism of Mahuang Lianqiao Chixiaodou Decoction(MHLQ) and its main active components in treating immunoglobin A nephropathy(IgAN). The rat model of IgAN was established by a combination of measures including gavage of bovine serum albumin, subcutaneous injection of carbon tetrachloride, and tail vein injection of lipopolysaccharide. The modeled rats were randomized into model, low-, medium-, and high-dose(1.773, 3.545, and 7.090 g·kg~(-1), respectively) MHLQ, phillyrin(PHI, 0.020 g·kg~(-1)), pseudoephedrine(PSE, 0.020 g·kg~(-1)), and losartan potassium(LP, 9.003 mg·kg~(-1)) groups, and Wistar rats were used as the control. Rats were administrated with corresponding drugs by gavage, and those in the control and model groups received an equal volume of normal saline. All the groups were treated for 4 consecutive weeks. Urine, serum, liver, and kidney samples were collected from rats in each group at the end of drug administration. The 24 h urine protein and renal function were examined, and staining was performed to observe the pathological changes in the renal tissue. The immunofluorescence assay was employed to detect the expression of IgA and complement C3/C3b/C3c in the renal tissue. Electron microscopy was employed to observe the ultrastructure of the renal tissue. Enzyme-linked immunosorbent assay was performed to determine the expression of complement C3 and sublytic C5b-9 in the serum and renal tissue. Western blot was performed to determine the expression levels of hepatic and renal complement C3/C3b/C3c, C5/C5a, C5b-9, and complement factor B(CFB). Immunohistochemistry(IHC) was employed to measure the expression of complement C3 in the renal tissue. The results showed that compared with the control group, the model group had elevated levels of blood urea nitrogen and serum creatinine, proliferation of glomerular mesangial cells and extracellular matrix, and glomerular deposition of IgA immune complexes or electron-dense material. In addition, the model group showcased increased serum C3 levels and up-regulated expression of CFB, C3/C3b/C3c, C5/C5a, and C5b-9 in the renal tissue and C3/C3b/C3c and C5b-9 in the hepatic tissue. After treatment with MHLQ and its active components, all of the above indexes were reversed. In conclusion, MHLQ and its active components can improve the renal function and reduce the deposition of immune complexes and pathological damage in the renal tissue of the rat model of IgAN by inhibiting the alternative pathway complement activation.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Glomerulonephritis, IGA/genetics* ; Rats ; Male ; Disease Models, Animal ; Rats, Wistar ; Complement Activation/drug effects* ; Kidney/immunology* ; Humans

Sepsis-associated coagulopathy refers to extensive coagulation activation accompanied by a high risk of bleeding and organ failure. In severe cases, it is manifested as disseminated intravascular coagulation (DIC) and leads to multiple organ dysfunction syndrome (MODS). Complement is an important component of the innate immune system and plays an important role in defending against invasion of pathogenic microorganisms. The early pathological process of sepsis involves excessive activation of the complement system, which forms an extremely complex network through interactions with the coagulation, kinin and fibrinolytic system, amplifying and exacerbating the systemic inflammatory response. In recent years, it has been suggested that uncontrolled complement activation system can exacerbate sepsis-associated coagulation dysfunction or even DIC, indicating the potential value of intervening in the complement system in the treatment of septic DIC, and related research progress is reviewed in this article in order to provide new ideas for the discovery of sepsis-associated coagulopathy therapy drugs.
Humans ; Blood Coagulation Disorders ; Complement Activation ; Blood Coagulation ; Multiple Organ Failure ; Sepsis

CD55 Antigens ; Complement Activation ; Humans ; Membrane Cofactor Protein ; Pemphigoid, Bullous ; Recombinant Fusion Proteins

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) involves dysregulation of the complement system, but whether this also occurs in thrombotic thrombocytopenic purpura (TTP) remains unclear. Although these conditions are difficult to differentiate clinically, TTP can be distinguished by low (<10%) ADAMTS13 activity. The aim was to identify the differences in complement activation products between TTP and aHUS and investigate ADAMTS13 activity as a prognostic factor in aHUS. METHODS: We analyzed patients with thrombotic microangiopathy diagnosed as TTP (N=48) or aHUS (N=50), selected from a Korean registry (N=551). Complement activation products in the plasma samples collected from the patients prior to treatment and in 40 healthy controls were measured by ELISA. RESULTS: The levels of generalized (C3a), alternate (factor Bb), and terminal (C5a and C5b-9) markers were significantly higher (all P<0.01) in the patients than in the healthy controls. Only the factor Bb levels significantly differed (P=0.008) between the two disease groups. In aHUS patients, high normal ADAMTS13 activity (≥77%) was associated with improved treatment response (OR, 6.769; 95% CI, 1.605–28.542; P=0.005), remission (OR, 6.000; 95% CI, 1.693–21.262; P=0.004), exacerbation (OR, 0.242; 95% CI, 0.064–0.916; P=0.031), and disease-associated mortality rates (OR, 0.155; 95% CI, 0.029–0.813; P=0.017). CONCLUSION: These data suggest that complement biomarkers, except factor Bb, are similarly activated in TTP and aHUS patients, and ADAMTS13 activity can predict the treatment response and outcome in aHUS patients.
Atypical Hemolytic Uremic Syndrome ; Biomarkers ; Complement Activation ; Complement System Proteins ; Enzyme-Linked Immunosorbent Assay ; Humans ; Mortality ; Plasma ; Purpura, Thrombotic Thrombocytopenic ; Thrombotic Microangiopathies

C3 glomerulopathy is a renal disorder involving dysregulation of alternative pathway complement activation. In most instances, a membranoproliferative pattern of glomerular injury with a prevalence of C3 deposition is observed by immunofluorescence microscopy. Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are subclasses of C3 glomerulopathy that are distinguishable by electron microscopy. Highly electron-dense transformation of glomerular basement membrane is characteristic of DDD. C3GN should be differentiated from post-infectious glomerulonephritis and other immune complex-mediated glomerulonephritides showing C3 deposits.
Complement Activation ; Complement Pathway, Alternative ; Dichlorodiphenyldichloroethane ; Glomerular Basement Membrane ; Glomerulonephritis ; Glomerulonephritis, Membranoproliferative ; Microscopy, Electron ; Microscopy, Fluorescence ; Pathology ; Prevalence

The complement system is an innate immune defense machinery comprising components that deploy rapid immune responses and provide efficient protection against foreign invaders and unwanted host elements. The complement system is activated upon recognition of pathogenic microorganisms or altered self-cells by exclusive pattern recognition molecules (PRMs), such as collectins, ficolins and pentraxins. Recent accumulating evidence shows that the different classes of effector PRMs build up a co-operative network and exert synergistic effects on complement activation. In this review, we describe our updated view of the crosstalk between previously unlinked PRMs in complement activation and the potential pathogenic effects during infection and inflammation.
Collectins ; Complement Activation* ; Complement System Proteins* ; Inflammation

OBJECTIVETo investigate the action of Shen-Fu Injection (SFI) in regulating the expression of the serum complements and inflammatory cytokines synthesized and released in response to the stress of global ischemia accompanying cardiac arrest (CA) and resuscitation.

METHODSThirty pigs were randomly divided into the sham (n=6) and 3 returns of spontaneous circulation (ROSC) groups (n=24). After 8-min untreated ventricular fibrillation and 2-min basic life support, 24 pigs of the ROSC groups were randomized into three groups (n=8 per group), which received central venous injection of SFI (SFI group), epinephrine (EP group), or saline (SA group). Hemodynamic status and blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 12, and 24 h after ROSC.

RESULTSSerum concentrations of specific activation markers of the complement system C3, C4 and C5b-9 were increased during cardiopulmonary resuscitation through 24 h after ROSC. There were intense changes of various pro-inflammatory cytokines and anti-inflammatory cytokines as early as 0.5 h after CA. Compared with the EP and SA groups, SFI treatment reduced the proinflammatory cytokines levels of interleukin (IL)-6, IL-8 and tumor necrosis factor α (TNF-α, P<0.05), and increased the anti-inflammatory cytokine levels of IL-4 and IL-10 (P<0.05). Further, SFI treatment decreased the values of C3, C4 and C5b-9 compared with the EP and SA groups.

CONCLUSIONSSFI, derived from the ancient Chinese medicine, has significant effects in attenuating post-resuscitation immune dysfunction by modulating the expression of complements and cytokines levels. The current study provided an experimental basis for the clinical application of a potential pharmacologic target for post resuscitation immune dysfunction.

Aconitine ; chemistry ; pharmacology ; Animals ; Cardiopulmonary Resuscitation ; Complement Activation ; drug effects ; Complement System Proteins ; metabolism ; Cytokines ; blood ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Ginsenosides ; chemistry ; pharmacology ; Hemodynamics ; drug effects ; Inflammation Mediators ; metabolism ; Injections ; Male ; Models, Animal ; Oxygen ; metabolism ; Survival Analysis ; Sus scrofa

The complement system is part of the innate immune response and as such defends against invading pathogens, removes immune complexes and damaged self-cells, aids organ regeneration, confers neuroprotection, and engages with the adaptive immune response via T and B cells. Complement activation can either benefit or harm the host organism; thus, the complement system must maintain a balance between activation on foreign or modified self surfaces and inhibition on intact host cells. Complement regulators are essential for maintaining this balance and are classified as soluble regulators, such as factor H, and membrane-bound regulators. Defective complement regulators can damage the host cell and result in the accumulation of immunological debris. Moreover, defective regulators are associated with several autoimmune diseases such as atypical hemolytic uremic syndrome, dense deposit disease, age-related macular degeneration, and systemic lupus erythematosus. Therefore, understanding the molecular mechanisms by which the complement system is regulated is important for the development of novel therapies for complement-associated diseases.
Adaptive Immunity ; Antigen-Antibody Complex ; Autoimmune Diseases ; Autoimmunity ; B-Lymphocytes ; Complement Activation ; Complement Factor H ; Complement System Proteins* ; Glomerulonephritis, Membranoproliferative ; Hemolytic-Uremic Syndrome ; Immunity, Innate ; Lupus Erythematosus, Systemic ; Macular Degeneration ; Physiology* ; Regeneration

Allergic reactions caused by traditional Chinese medicine injections (TCMIs) become a greatest concern in the clinic application safety. The integral animal evaluation method commonly used in the preclinical evaluation for allergic reactions of TCMIs was not sensitive, specific, quick and objective in observation indexes. Therefore, more researchers have paid attention to the in vitro test method for evaluating allergic reactions induced by TCMIs. Currently, the methods for evaluating allergic reactions induced by TCMIs are mainly targeted at type I allergic reaction and anaphylactic reaction, with only a few in vitro methods for evaluating type II allergic reaction. In this paper, researchers summarized relevant literatures published about evaluation methods for allergic reactions induced by TCMIs in recent years.
Animals ; Complement Activation ; Drug Hypersensitivity ; diagnosis ; etiology ; Humans ; Injections ; Medicine, Chinese Traditional ; adverse effects

Complement Activation ; Humans ; Thrombosis ; immunology