| 1. |
- Chaban, Viktoriia, et al.
(författare)
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Escherichia coli-induced inflammatory responses are temperature-dependent in human whole blood ex vivo
- 2023
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Ingår i: Molecular Immunology. - : Elsevier. - 0161-5890 .- 1872-9142. ; 157, s. 70-77
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Tidskriftsartikel (refereegranskat)abstract
- Systemic inflammatory conditions are often associated with hypothermia or hyperthermia. Therapeutic hypothermia is used in post-cardiac arrest and some other acute diseases. There is a need for more knowledge concerning the effect of various temperatures on the acute inflammatory response. The complement system plays a crucial role in initiating the inflammatory response. We hypothesized that temperatures above and below the physiologic 37 & DEG;C affect complement activation and cytokine production ex vivo. Lepirudin-anticoagulated human whole blood from 10 healthy donors was incubated in the presence or absence of Escherichia coli at different temperatures (4 & DEG;C, 12 & DEG;C, 20 & DEG;C, 33 & DEG;C, 37 & DEG;C, 39 & DEG;C, and 41 & DEG;C). Complement activation was assessed by the terminal C5b-9 complement complex (TCC) and the alternative convertase C3bBbP using ELISA. Cytokines were measured using a 27-plex assay. Granulocyte and monocyte activation was evaluated by CD11b surface expression using flow cytometry. A consistent increase in complement activation was observed with rising temperature, reaching a maximum at 41 & DEG;C, both in the absence (C3bBbP p < 0.05) and presence (C3bBbP p < 0.05 and TCC p < 0.05) of E. coli. Temperature alone did not affect cytokine production, whereas incubation with E. coli significantly increased cytokine levels of IL-18, IL-2, IL-6, IL-8, IFN-& gamma;, and TNF at temperatures > 20 & DEG;C. Maximum increase occurred at 39 & DEG;C. However, a consistent decrease was observed at 41 & DEG;C, significant for IL-18 (p = 0.003). Granulocyte CD11b displayed the same temperature-dependent pattern as cytokines, with a corresponding increase in endothelial cell apoptosis and necrosis. Thus, blood temperature differentially determines the degree of complement activation and cytokine release.
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| 2. |
- de Boer, Eline, et al.
(författare)
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Synthetic Oligodeoxynucleotide CpG Motifs Activate Human Complement through Their Backbone Structure and Induce Complement-Dependent Cytokine Release
- 2022
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Ingår i: Journal of Immunology. - : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 209:9, s. 1760-1767
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial and mitochondrial DNA, sharing an evolutionary origin, act as danger-associated molecular patterns in infectious and sterile inflammation. They both contain immunomodulatory CpG motifs. Interactions between CpG motifs and the complement system are sparsely described, and mechanisms of complement activation by CpG remain unclear. Lepirudin-anticoagulated human whole blood and plasma were incubated with increasing concentrations of three classes of synthetic CpGs: CpG-A, -B, and -C oligodeoxynucleotides and their GpC sequence controls. Complement activation products were analyzed by immunoassays. Cytokine levels were determined via 27-plex beads-based immunoassay, and CpG interactions with individual complement proteins were evaluated using magnetic beads coated with CpG-B. In whole blood and plasma, CpG-B and CpG-C (p < 0.05 for both), but not CpG-A (p > 0.8 for all), led to time- and dose-dependent increase of soluble C5b-9, the alternative complement convertase C3bBbP, and the C3 cleavage product C3bc. GpC-A, -B, and -C changed soluble fluid-phase C5b-9, C3bBbP, and C3bc to the same extent as CpG-A, -B, and -C, indicating a DNA backbone-dependent effect. Dose-dependent CpG-B binding was found to C1q (r = 0.83; p 5 0.006) and factor H (r = 0.93; p < 0.001). The stimulatory complement effect was partly preserved in C2-deficient plasma and completely preserved in MASP-2-deficient serum. CpG-B increased levels of IL-1 beta, IL-2, IL-6, IL-8, MCP-1, and TNF in whole blood, which were completely abolished by inhibition of C5 and C5aR1 (p < 0.05 for all). In conclusion, synthetic analogs of bacterial and mitochondrial DNA activate the complement system via the DNA backbone. We suggest that CpG-B interacts directly with classical and alternative pathway components, resulting in complement-C5aR1-dependent cytokine release.
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| 3. |
- Ericsson, Anders B., et al.
(författare)
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Correlation between a Mid-ventricular Volume Segment and Global Left Ventricular Volume Measured by the Conductance Catheter
- 2001
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 35:2, s. 129-135
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Tidskriftsartikel (refereegranskat)abstract
- Objectives-To investigate whether acute volume changes in single volume segments of the left ventricle can be correlated with global volume changes. If so, changes in global volume might be predicted from changes in segmental volumes. Design-Volume changes were recorded in six pigs in five intraventricular segments, from apex to heart base, using the conductance catheter (at baseline, after 60 min of apical ischaemia, during preload reduction and afterload increase). A computer algorithm was created to calculate the instantaneous absolute difference between the curve shape of global and normalized segmental volume as a percentage of global stroke volume. Results-For a mid-cardiac volume segment constituting 34 (14-39)% [median (range)] of global stroke volume, the mean difference over a cardiac cycle was 4 (1-8)% at baseline. Apical ischaemia resulted in apical dyskinesia, but did not influence the mid-cardiac segment. Conclusions-The volume curve from a segment at mid-cardiac level seems to be a good estimator of the global volume curve, thus giving a foundation for estimation of global volume changes from such a segment.
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| 4. |
- Svenmarker, Staffan, 1951-
(författare)
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Heparin coating and cardiotomy suction in cardiopulmonary bypass
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present thesis addresses various means of reducing inflammatory responses associated with cardiopulmonary bypass (CPB) and retransfusion of pericardial suction blood (PSB) during cardiac surgery. Four (I-IV) prospective randomised controlled clinical trials comprising 475 patients were performed in the following areas: effects of heparin coating on measures of clinical outcome and memory function (I, II), inflammatory reactions in PSB and its systemic effects after retransfusion using cardiotomy suction or cell salvage (III) and effects of retransfusion of PSB on memory function and release patterns of protein S100B (IV). The use of heparin coated CPB-circuits was associated with a decrease of postoperative blood loss (I, II), transfusion requirements (II), shorter stay in hospital (I) decreased postoperative ventilator time (I), lower incidences of atrial fibrillation (II) and neurological deviations (I), reduction in releases of protein S100B (I, II) and lower postoperative creatinine elevation (I, II). PSB contained high concentrations of cytokines, complements, myeloperoxidase, free plasma haemoglobin and protein S100B (III, IV). Retransfusion using cardiotomy suction increased the systemic concentrations of free plasma haemoglobin and protein S100B, whereas retransfusion using cell salvage caused no detectable systemic effects (III, IV). CPB was associated with a small but significant release of protein S100B, despite elimination of PSB-contained protein S100B using cell salvage (IV). Subtle signs of impaired memory function were identified that were not associated with the use of heparin coated CPB-circuits (I, II) or retransfusion of PSB (IV). Key words: cardiopulmonary bypass, oxygenators, heparin, S100 proteins, blood loss, haemostasis, memory, outcome and process assessment.
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