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1.
J Immunol Methods ; 531: 113709, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38862098

ABSTRACT

The complement system plays a crucial role in orchestrating the activation and regulation of inflammation within the human immune system. Three distinct activation pathways-classical, lectin, and alternative-converge to form the common lytic pathway, culminating in the formation of the membrane-attacking complex that disrupts the structure of pathogens. Dysregulated complement system activity can lead to tissue damage, autoimmune diseases, or immune deficiencies. In this study, the antimicrobial activity of human serum was investigated by using a bioluminescent microbe probe, Escherichia coli (pEGFPluxABCDEamp). This probe has previously been used to determine the antimicrobial activity of complement system and the polymorphonuclear neutrophils. In this study, blocking antibodies against key serum activators and components, including IgG, complement component 1q, factor B, and properdin, were utilized. The influence of body temperature and acute phase proteins, such as C reactive protein (CRP) and serum amyloid alpha (SAA), on the complement system was also examined. The study reveals the critical factors influencing complement system activity and pathway function. Alongside crucial factors like C1q and IgG, alternative pathway components factor B and properdin played pivotal roles. Results indicated that the alternative pathway accounted for approximately one third of the overall serum antimicrobial activity, and blocking this pathway disrupted the entire complement system. Contrary to expectations, elevated body temperature during inflammation did not enhance the antimicrobial activity of human serum. CRP demonstrated complement activation properties, but at higher physiological concentrations, it exhibited antagonistic tendencies, dampening the response. On the other hand, SAA enhanced the serum's activity. Overall, this study sheds a light on the critical factors affecting both complement system activity and pathway functionality, emphasizing the importance of a balanced immune response.


Subject(s)
Body Temperature , C-Reactive Protein , Complement Activation , Complement C1q , Complement Factor B , Properdin , Serum Amyloid A Protein , Humans , C-Reactive Protein/metabolism , C-Reactive Protein/immunology , Complement C1q/immunology , Complement C1q/metabolism , Serum Amyloid A Protein/metabolism , Serum Amyloid A Protein/immunology , Properdin/immunology , Properdin/metabolism , Complement Factor B/metabolism , Complement Factor B/immunology , Body Temperature/immunology , Escherichia coli/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology
2.
Heliyon ; 10(2): e24104, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38293363

ABSTRACT

Indoor exposure to microbial growth, caused by moisture damage, has been an established health risk for several decades. It is likely that a damp indoor environment contains biological pollutants that trigger both the innate and adaptive branches of the immune system. In this study, we investigated the association between moisture damage related microbial exposure and serum C3a, C5a and CRP concentrations in Finnish adults. Serum C3a and CRP concentrations were elevated in individuals exposed to moisture damage and microbial growth in an indoor air environment. The elevated concentrations may be due to environmental factors present in moisture-damaged buildings. Complement activation and the resulting proinflammatory cleavage products may be a driving factor in inflammatory responses following exposure to indoor moisture damage and related microbial growth.

3.
Life (Basel) ; 12(2)2022 Jan 21.
Article in English | MEDLINE | ID: mdl-35207450

ABSTRACT

Acclimation of cyanobacterium Synechocystis sp. PCC6803 to suboptimal conditions is largely dependent on adjustments of gene expression, which is highly controlled by the σ factor subunits of RNA polymerase (RNAP). The SigB and SigD σ factors are close homologues. Here we show that the sigB and sigD genes are both induced in high light and heat stresses. Comparison of transcriptomes of the control strain (CS), ΔsigB, ΔsigD, ΔsigBCE (containing SigD as the only functional group 2 σ factor), and ΔsigCDE (SigB as the only functional group 2 σ factor) strains in standard, high light, and high temperature conditions revealed that the SigB and SigD factors regulate different sets of genes and SigB and SigD regulons are highly dependent on stress conditions. The SigB regulon is bigger than the SigD regulon at high temperature, whereas, in high light, the SigD regulon is bigger than the SigB regulon. Furthermore, our results show that favoring the SigB or SigD factor by deleting other group 2 σ factors does not lead to superior acclimation to high light or high temperature, indicating that all group 2 σ factors play roles in the acclimation processes.

4.
Innate Immun ; 27(1): 15-22, 2021 01.
Article in English | MEDLINE | ID: mdl-33287602

ABSTRACT

In this comparative study, serum complement system antimicrobial activity was measured from 159 serum samples, taken from individuals from microbe-damaged (70 samples) and from reference buildings (89 samples). Antimicrobial activity was assessed using a probe-based bacterial Escherichia coli-lux bioluminescence system and comparison was made at a group level between the experimental and reference group. The complement activity was higher in users of microbe-damaged buildings compared with the reference group and the significant (P < 0.001) increase in activity was found in the classical reaction pathway. This study strengthens our notion that exposure to indoor-related microbe damage increases the risk for systemic subclinical inflammation and creates a health risk for building users.


Subject(s)
Air Microbiology , Blood Bactericidal Activity/immunology , Complement System Proteins/immunology , Bacteria , Bacterial Load , Colony Count, Microbial , Complement Pathway, Alternative , Complement Pathway, Classical , Escherichia coli , Fungi , Humans , Reference Values , Sick Building Syndrome/immunology , Sick Building Syndrome/microbiology
5.
Sci Total Environ ; 698: 134335, 2020 Jan 01.
Article in English | MEDLINE | ID: mdl-31518785

ABSTRACT

Moisture-indicative microbes in buildings are associated with a variety of symptoms, ranging from mild irritation to severe clinical illnesses. These symptoms are caused principally by dried, dormant and dead microbe material like spores, mycelium and microbe metabolites, leading to the activation of the immune system and formation of the antigen-specific immunoglobulins. This activation presumably takes place through the respiratory track and is a normal immune reaction against pathogenic invaders. During continuous exposure, a prolonged state of inflammation will follow, and this forms a considerable health risk for a building's occupant. A new ELISA system utilizing spores from two species Streptomyces albus and Aspergillus versicolor as an antigen was developed to reveal the related immunological processes. In 159 persons, microbial exposure was observed to increase the levels of spore-specific IgG, IgG1 and IgG3 serum antibody levels of individuals residing in microbe-dense buildings compared with the control reference buildings. No differences were detected in the levels of S. albus- and A. versicolor-specific serum IgA or IgM levels.


Subject(s)
Air Microbiology , Air Pollution, Indoor/analysis , Aspergillus , Environmental Exposure/analysis , Immunoglobulin G/metabolism , Spores, Fungal , Streptomyces , Environmental Exposure/statistics & numerical data , Enzyme-Linked Immunosorbent Assay , Humans
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