Contribution Of Complement Activation Research Articles

Elevated Complement Activation Fragments and C1q-Binding Circulating Immune Complexes in Varied Phases of Chikungunya Virus Infection.

Chikungunya virus (CHIKV) is a causative agent of a disease continuum, ranging from an acute transient chikungunya fever to chronic incapacitating viral arthralgia. The interaction between anti-CHIKV antibodies and the complement system has recently received attention. However, the contribution of complement activation in CHIKV-induced pathologies has not been fully elucidated. The present study was undertaken to delineate the possible contribution of complement activation in CHIKV-induced disease progression. In this study, using plasma specimens of chikungunya patients in the acute, chronic, and recovered phases of infection, we explicated the involvement of complement activation in CHIKV disease progression by ELISAs and Bio-Plex assays. Correlation analysis was carried out to demonstrate interrelation among C1q-binding IgG-containing circulating immune complexes (CIC-C1q), complement activation fragments (C3a, C5a, sC5b-9), and complement-modulated pro-inflammatory cytokines (IL-1β, IL-18,IL-6, andTNF-α). We detected elevated complement activation fragments, CIC-C1q, and complement-modulated cytokines in the varied patient groups compared with the healthy controls, indicating persistent activation of the complement system. Furthermore, we observed statistically significant correlations among CIC-C1q with complement activation fragments and C3a with complement modulatory cytokines IL-1β, IL-6, and IL-18 during the CHIKV disease progression. Taken together, the current data provide insight into the plausible association between CICs, complement activation, subsequent complement modulatory cytokine expression, and CHIKV etiopathology.

Contribution of Anaphylatoxins to Allergic Inflammation in Human Lungs

The contribution of complement activation to allergic asthma remains controversial. In order to elucidate the role played by the complement split products, anaphylatoxins C3a and C5a, we evaluated their effects on production of cysteinyl-leukotrienes (cysLTs) by human lung fragments following an anaphylactic reaction. The lung tissues obtained from two patients with lung cancer showed C5aR-, C5L2R-, and C3aR-mRNA expression. When the chopped lung fragments passively sensitized with human IgE were incubated with anti-human IgE antibody, a significant amount of cysLTs was generated in comparison with the control (without anti-IgE antibody). The co-addition of human C5a at doses of 0.1 to 10 ng/ml to the anti-IgE antibody potentiated cysLT production. The response was bell-shaped in distribution, significant, and peaked at a C5a concentration of 1 ng/ml. The co-addition of human C3a up to 1,000 ng/ml seemed to increase cysLT production, but not to any significant extent. A novel C5a receptor complementary peptide, acetylated peptide A, dose-dependently inhibited cysLT production by the human lung fragments following the anaphylactic reaction in the presence of 1 ng/ml C5a. However, this peptide did not inhibit cysLT production in the presence of 100 ng/ml C3a. It is suggested that the anaphylatoxin C5a potentiates cysLT production in human lung tissues and contributes to allergic inflammation in disorders such as asthma, thus acetylated peptide A may be useful for suppressing allergic inflammation in the lungs.

Pathogenic mechanisms in membranoproliferative glomerulonephritis

This review considers new information on the pathogenesis of a long recognized and poorly understood form of glomerular injury, membranoproliferative glomerulonephritis. This disease has received growing attention as it is the principal renal manifestation of hepatitis C virus infection, which has become pandemic worldwide. This review briefly describes three murine models of membranoproliferative glomerulonephritis suitable for pathogenesis studies. We consider recent evidence implicating innate immune mechanisms in immune and autoimmune-mediated glomerulonephritis, and recent data pointing to the alternative pathway of complement activation in the amplification of glomerulonephritic injury. Understanding the contribution of complement activation and innate immunity to the evolution of membranoproliferative glomerulonephritis promises to provide new therapeutic targets for this disease. Inhibitors of the complement cascade are already being tested in clinical trials as therapeutic interventions for some human glomerular diseases. Successful tests of this approach in membranoproliferative glomerulonephritis are still awaited. Our understanding of how the innate immune system modulates glomerulonephritis is still in an early stage, and future studies should be directed at identifying targets and specific interventions that may also benefit patients with this disease.

Contribution of complement activation to the rise in blood levels of 6- oxo-prostaglandin F1α during endotoxin-induced hypotension in rabbits

Contribution of complement activation to the rise in blood levels of 6- oxo-prostaglandin F1α during endotoxin-induced hypotension in rabbits