scholarly journals Simple Method To Distinguish between Primary and Secondary C3 Deficiencies

2003 ◽  
Vol 10 (2) ◽  
pp. 216-220
Author(s):  
Marlene Pereira de Carvalho Florido ◽  
Patrícia Ferreira de Paula ◽  
Lourdes Isaac
Keyword(s):  
Human Serum ◽  
Complement System ◽  
Factor H ◽  
Normal Human Serum ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Factor B ◽  
Alternative Complement ◽  
Normal Human ◽  
The Complement System

ABSTRACT Due to the increasing numbers of reported clinical cases of complement deficiency in medical centers, clinicians are now more aware of the role of the complement system in the protection against infections caused by microorganisms. Therefore, clinical laboratories are now prepared to perform a number of diagnostic tests of the complement system other than the standard 50% hemolytic component assay. Deficiencies of alternative complement pathway proteins are related to severe and recurrent infections; and the application of easy, reliable, and low-cost methods for their detection and distinction are always welcome, notably in developing countries. When activation of the alternative complement pathway is evaluated in hemolytic agarose plates, some but not all human sera cross-react to form a late linear lysis. Since the formation of this linear lysis is dependent on C3 and factor B, it is possible to use late linear lysis to routinely screen for the presence of deficiencies of alternative human complement pathway proteins such as factor B. Furthermore, since linear lysis is observed between normal human serum and primary C3-deficient serum but not between normal human serum and secondary C3-deficient serum caused by the lack of factor H or factor I, this assay may also be used to discriminate between primary and secondary C3 deficiencies.

scholarly journals Toxoplasma Infection Induces Sustained Up-Regulation of Complement Factor B and C5a Receptor in the Mouse Brain via Microglial Activation: Implication for the Alternative Complement Pathway Activation and Anaphylatoxin Signaling in Cerebral Toxoplasmosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Noriko Shinjyo ◽  
Kenji Hikosaka ◽  
Yasutoshi Kido ◽  
Hiroki Yoshida ◽  
Kazumi Norose
Keyword(s):  
Complement System ◽  
Microglial Activation ◽  
Brain Parenchyma ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Factor B ◽  
Alternative Complement ◽  
Anaphylatoxin C3a ◽  
The Complement System ◽  
The Brain

Toxoplasma gondii is a neurotropic protozoan parasite, which is linked to neurological manifestations in immunocompromised individuals as well as severe neurodevelopmental sequelae in congenital toxoplasmosis. While the complement system is the first line of host defense that plays a significant role in the prevention of parasite dissemination, Toxoplasma artfully evades complement-mediated clearance via recruiting complement regulatory proteins to their surface. On the other hand, the details of Toxoplasma and the complement system interaction in the brain parenchyma remain elusive. In this study, infection-induced changes in the mRNA levels of complement components were analyzed by quantitative PCR using a murine Toxoplasma infection model in vivo and primary glial cells in vitro. In addition to the core components C3 and C1q, anaphylatoxin C3a and C5a receptors (C3aR and C5aR1), as well as alternative complement pathway components properdin (CFP) and factor B (CFB), were significantly upregulated 2 weeks after inoculation. Two months post-infection, CFB, C3, C3aR, and C5aR1 expression remained higher than in controls, while CFP upregulation was transient. Furthermore, Toxoplasma infection induced significant increase in CFP, CFB, C3, and C5aR1 in mixed glial culture, which was abrogated when microglial activation was inhibited by pre-treatment with minocycline. This study sheds new light on the roles for the complement system in the brain parenchyma during Toxoplasma infection, which may lead to the development of novel therapeutic approaches to Toxoplasma infection-induced neurological disorders.

scholarly journals The Impact of Graphite Oxide Nanocomposites on the Antibacterial Activity of Serum

2021 ◽  
Vol 22 (14) ◽  
pp. 7386
Author(s):  
Katarzyna Dorota Morka ◽  
Maciej Wernecki ◽  
Anna Kędziora ◽  
Marta Książczyk ◽  
Bartłomiej Dudek ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Human Serum ◽  
Complement System ◽  
Graphite Oxide ◽  
Galleria Mellonella ◽  
Serum Proteins ◽  
Normal Human Serum ◽  
Normal Human ◽  
The Impact ◽  
The Complement System

Nanoparticles can interact with the complement system and modulate the inflammatory response. The effect of these interactions on the complement activity strongly depends on physicochemical properties of nanoparticles. The interactions of silver nanoparticles with serum proteins (particularly with the complement system components) have the potential to significantly affect the antibacterial activity of serum, with serious implications for human health. The aim of the study was to assess the influence of graphite oxide (GO) nanocomposites (GO, GO-PcZr(Lys)2-Ag, GO-Ag, GO-PcZr(Lys)2) on the antibacterial activity of normal human serum (NHS), serum activity against bacteria isolated from alveoli treated with nanocomposites, and nanocomposite sensitivity of bacteria exposed to serum in vitro (using normal human serum). Additionally, the in vivo cytotoxic effect of the GO compounds was determined with application of a Galleria mellonella larvae model. GO-PcZr(Lys)2, without IR irradiation enhance the antimicrobial efficacy of the human serum. IR irradiation enhances bactericidal activity of serum in the case of the GO-PcZr(Lys)2-Ag sample. Bacteria exposed to nanocomposites become more sensitive to the action of serum. Bacteria exposed to serum become more sensitive to the GO-Ag sample. None of the tested GO nanocomposites displayed a cytotoxicity towards larvae.

scholarly journals Complement 1 Inhibitor Is a Regulator of the Alternative Complement Pathway

2001 ◽  
Vol 194 (11) ◽  
pp. 1609-1616 ◽  
Author(s):  
Haixiang Jiang ◽  
Eric Wagner ◽  
Huamei Zhang ◽  
Michael M. Frank
Keyword(s):  
Human Serum ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Alternative Pathway ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Cobra Venom Factor ◽  
Factor B ◽  
Alternative Complement ◽  
Pathway Function ◽  
Cross Competition

We studied complement 1 inhibitor (C1-INH) as an inhibitor of the alternative complement pathway. C1-INH prevented lysis, induced by the alternative complement pathway, of paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes in human serum. It inhibited the binding of both factors B and C3 to PNH and rabbit erythrocytes and blocked the ability of factor B to restore alternative-pathway function in factor B–depleted serum. C1-INH did not bind to factors B or D but did bind to immobilized C3b and cobra venom factor (CVF), a C3b analogue. C1-INH prevented factor B from binding to CVF-coated beads and dissociated bound factor B from such beads. Factor B and C1-INH showed cross competition in binding to CVF-coated beads. Factor D cleaved factor B into Bb and Ba in the presence of C3b. Cleavage was markedly inhibited when C3b was preincubated with C1-INH. C1-INH inhibited the formation of CVFBb and decreased the C3 cleavage. Removal of C1-INH from serum, in the presence of Mg-EGTA with an anti–C1-INH immunoabsorbant, markedly increased alternative-pathway lysis. C1-INH interacts with C3b to inhibit binding of factor B to C3b. At physiologic concentrations, it is a downregulator of the alternative pathway convertase.

scholarly journals Complement Factor D as a Strategic Target for Regulating the Alternative Complement Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Jonathan Barratt ◽  
Ilene Weitz
Keyword(s):  
Complement System ◽  
Complement Activation ◽  
Alternative Pathway ◽  
Treatment Options ◽  
Underlying Disease ◽  
Alternative Complement Pathway ◽  
Complement Factor ◽  
Complement Pathway ◽  
Alternative Complement ◽  
The Complement System

The complement system is central to first-line defense against invading pathogens. However, excessive complement activation and/or the loss of complement regulation contributes to the development of autoimmune diseases, systemic inflammation, and thrombosis. One of the three pathways of the complement system, the alternative complement pathway, plays a vital role in amplifying complement activation and pathway signaling. Complement factor D, a serine protease of this pathway that is required for the formation of C3 convertase, is the rate-limiting enzyme. In this review, we discuss the function of factor D within the alternative pathway and its implication in both healthy physiology and disease. Because the alternative pathway has a role in many diseases that are characterized by excessive or poorly mediated complement activation, this pathway is an enticing target for effective therapeutic intervention. Nonetheless, although the underlying disease mechanisms of many of these complement-driven diseases are quite well understood, some of the diseases have limited treatment options or no approved treatments at all. Therefore, in this review we explore factor D as a strategic target for advancing therapeutic control of pathological complement activation.

scholarly journals The alternative complement pathway is activated in protoporphyria patients during sun exposure

2020 ◽  
Author(s):  
Francesca Granata ◽  
Lorena Duca ◽  
Valentina Brancaleoni ◽  
Silvia Fustinoni ◽  
Giacomo De Luca ◽  
...  
Keyword(s):  
Light Exposure ◽  
Alternative Pathway ◽  
Global Radiation ◽  
Protoporphyrin Ix ◽  
Sun Exposure ◽  
Factor H ◽  
Factor B ◽  
Alternative Complement ◽  
Differential Involvement ◽  
The Complement System

ABSTRACTThe homeostasis of tissues in chronic disease is an important function of the alternative pathway (AP) of the complement system (CS). However, if not controlled, it may also be detrimental to healthy cells.Protoporphyria (PP) is a rare disease that causes photosensitivity at the visible light due to the accumulation of Protoporphyrin-IX in the dermis. The aim of this study was to deep the knowledge about the involvement of AP in PP photoreaction.Global radiation and UV data were provided from regional agency of environmental protection (ARPA). Properdin, Factor H (FH) and C5 levels were assessed in the serum collected during winter and summer from 19 PP patients and 13 controls..Properdin in winter and summer reflected a positive increase compared to controls. The values in summer were higher than winter. The C5 results were altered only in summer. The outcome was reversed for FH: in the winter, it was higher compared to the summer. A positive correlation was reported between properdin and C3 in summer; a negative tendency between Factor B (FB) and FH was detected.This study substantiated the differential involvement of AP depending on the increase in light exposure during the season, which was demonstrated with ARPA data. The enhanced systemic response could justify the malaise sensation of patients after long light exposure and can be exploited to elucidate the new therapeutic approach.

scholarly journals Modulation of Renal Disease in MRL/lpr Mice Genetically Deficient in the Alternative Complement Pathway Factor B

2000 ◽  
Vol 164 (2) ◽  
pp. 786-794 ◽  
Author(s):  
Hiroshi Watanabe ◽  
Gérard Garnier ◽  
Antonella Circolo ◽  
Rick A. Wetsel ◽  
Phil Ruiz ◽  
...  
Keyword(s):  
Renal Disease ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Factor B ◽  
Alternative Complement
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