Finally, the expression of the topmost upregulated genes (<i>ARG1</i>, <i>IL1R2</i>, <i>ELANE</i>, <i>MMP9</i>) was quantified by reverse transcriptase-PCR (RT-PCR), and myeloperoxidase (<i>MPO</i>) expression was confirmed by immunohistochemistry (IHC) staining in the lungs of a well-established sepsis mouse model.
Our data provide proof-of-principle that 2-ClPA and 2-ClHDA induce powerful proinflammatory responses both in vitro and in vivo, suggesting the possibility that these chlorinated lipid products of the MPO/ hydrogen peroxide /chloride system may contribute to inflammation noted in neutrophil-dependent, myeloperoxidase-mediated pathologic states such as ischemia/reperfusion, hemorrhagic shock, and sepsis.
We measured plasma (n = 182) and urine (n = 118) activin A (a rapidly released cytosolic neutrophil protein), interleukin-8 (a chemotactic factor for neutrophils), myeloperoxidase (a neutrophil biomarker released in tissues), and interleukin-6 on intensive care unit admission (plasma and urine) and 24 hours later (plasma) in sepsis patients manifesting their first organ dysfunction between 24 hours preceding admission and the second calendar day in intensive care unit.
In an acute lung inflammation mouse model, an intratracheal (i.t.) eCS suppressed neutrophil infiltration, the expression of inflammatory cytokine genes, and MPO activity.In a sepsis mouse model, a single i.t. eCS was sufficient to significantly decrease mouse mortality.
We propose the flow cytometry detection of MPO/H3cit positive neutrophils and serum dsDNA as simple methods to quantify cellular and extracellular NET markers in patients with thrombosis and sepsis.
Wistar rats 2month-old were subjected to sepsis and 60 and 90days after were submitted to the new object recognition test and brain was removed to the determination of cytokines, myeloperoxidase (MPO) activity, amyloid-beta peptide (Aβ) and immunohistochemistry markers of microglial activation.
Aspt and Not treatment also reduced the plasma levels of NO, TNF-α, IL-6, and MPO and reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defence system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in the kidney tissues.
At enrollment, sepsis was associated with significant increases in the expression of mRNAs related to redox metabolism (myeloperoxidase, 64-fold; PRDX3, 2.6-fold; SOD2, 2.2-fold) and redox-responsive genes (FOXM1, 21-fold; SELS, 16-fold; GLRX2, 3.4-fold).
NETs in patients with NET-associated diseases, that is, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA) and sepsis, were characterised in sandwich ELISAs employing antibodies against myeloperoxidase (MPO) and N-terminal histone tails as detecting and capturing antibodies, respectively.
Augmented levels of oxidants were found in sepsis as demonstrated by DMPO nitrone adduct formation and plasma MPO level activity (1.37 ± 0.51 in sepsis vs 0.405 ± 0.16 in control subjects).
Pretreatment with ZSCLE (100, 200, and 300 mg/kg) restored the normal heart rate (HR); decreased the elevated levels of malondialdehyde; the activity of myeloperoxidase, nitric oxide (NO), and inducible NO synthase; and the expression of nuclear factor kappa B (NF-κB), but increased the content of glutathione and antioxidant enzyme activities in mice with sepsis.
Since neutrophil myeloperoxidase (MPO) activity leads to increased plasma 2-chlorofatty acid (2-ClFA) levels, we hypothesized that plasma concentrations of 2-ClFAs would associate with ARDS and mortality in subjects with sepsis.
Lower ARE (153.24 vs. 264.32U/L; p<0.001), lower CLP (80.58 vs. 97.98U/L; p=0.032), lower MPO (91.24 vs. 116.55U/L; p=0.023), and higher CAT levels (256.5 vs.145.5kU/L; p=0.003) were determined in the sepsis group as compared to the control group.
Moreover, significant lower levels of TNF-<i>α</i>, IL-6, bacterial loads, MPO, and ROS were discovered in the KO-CLP sepsis group in contrast to the WT-CLP sepsis group.
Nicotine injection prior to sepsis depressed MPO activity in all tissues and reduced MDA levels except for the lung, while GSH levels were elevated only in the hepatic and ileal tissues.
Activation of leukocytes and in particular polymorphonuclear neutrophils (PMN) has emerged as a critical confounder in the pathophysiology of cardiovascular disease: Myeloperoxidase (MPO), one of the principal proteins hosted in and secreted by activated PMN, has been mechanistically linked to endothelial and left ventricular (LV) dysfunction in rodent models of sepsis and ischemic cardiomyopathy.