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

BACKGROUND: In vitro levels of complement C3 and C4 proteins are sensitive to storage conditions. To avoid in vitro complement activation when testing is delayed, serum should be frozen at -20degrees C within 2 hr of venipuncture. However, this is impractical in routine laboratory work. Therefore, we investigated alterations in C3 and C4 levels in refrigerated specimens over time and derived formulae to estimate initial levels of complement concentrations in delayed testing. METHODS: Ten fresh specimens were measured for C3 and C4 concentrations and were refrigerated at 4degrees C. We measured C3 and C4 levels in refrigerated samples daily for 4 days using an automated nephelometer (Beckman Coulter Inc., USA). RESULTS: C3 and C4 levels were significantly increased over time in refrigerated specimens (P<0.001, P<0.001, respectively). The increments in C3 and C4 levels were described by the equations: C3 (mg/dL)=3.55x+87.18 (r=0.9909), and C4 (mg/dL)=0.72x+22.3 (r=0.9395), where x=the number of days samples were refrigerated before testing. Increases in C3 and C4 concentrations were described on a percentage basis by the equations: DeltaC3 (%)=4.14x+1.07 (r=0.9903), and DeltaC4 (%)=3.57x+2.48 (r=0.9405). CONCLUSIONS: As the measured C3 and C4 concentrations increased by 3.55 mg/dL (4.1%) and 0.72 mg/dL (3.6%) per day in refrigerated specimens, the levels of C3 and C4 should be adjusted in delayed testing. We proposed that the formulae presented be used to back-calculate initial levels of C3 and C4 concentrations.
Complement Activation ; Complement C3* ; Complement C4 ; Complement System Proteins ; Phlebotomy

K/BxN serum can transfer arthritis to normal mice owing to the abundant autoantibodies it contains, which trigger innate inflammatory cascades in joints. Little is known about whether gut-residing microbes affect host susceptibility to autoantibody-mediated arthritis. To address this, we fed C57BL/6 mice with water containing a mixture of antibiotics (ampicillin, vancomycin, neomycin, and metronidazol) for 2 weeks and then injected them with K/BxN serum. Antibiotic treatment significantly reduced the amount of bacterial genomic DNA isolated from fecal samples, in particular a gene encoding 16S ribosomal RNA derived from segmented filamentous bacteria. Arthritic signs, as indicated by the arthritic index and ankle thickness, were significantly attenuated in antibiotic-treated mice compared with untreated controls. Peyer's patches and mesenteric lymph nodes from antibiotic-treated mice contained fewer IL-17-expressing cells than those from untreated mice. Antibiotic treatment reduced serum C3 deposition in vitro via the alternative complement pathway. IL-17-/- congenic C57BL/6 mice were less susceptible to K/BxN serum-transferred arthritis than their wild-type littermates, but were still responsive to treatment with antibiotics. These results suggest that gut-residing microbes, including segmented filamentous bacteria, induce IL-17 production in GALT and complement activation via the alternative complement pathway, which cause the host to be more susceptible to autoantibody-mediated arthritis.
Animals ; Ankle ; Anti-Bacterial Agents ; Arthritis* ; Autoantibodies ; Bacteria ; Complement Activation ; Complement Pathway, Alternative ; DNA ; Genes, vif ; Interleukin-17 ; Joints ; Lymph Nodes ; Mice ; Neomycin ; Peyer's Patches ; RNA, Ribosomal, 16S ; Vancomycin ; Water