Delayed neutrophil apoptosis has been demonstrated in sepsis and may contribute to organ damage. It has recently been proposed that apolipoprotein L (ApoL) may be involved in programmed cell death, but the expression and functions of ApoLs in leukocytes (especially neutrophils) during sepsis and other inflammatory conditions are currently unknown. In this prospective observational study in a 36-bed university hospital medicosurgical intensive care unit (ICU), we included 78 adult ICU patients with (n = 41) or without (n = 37) sepsis and 47 healthy volunteers. We analyzed ApoL mRNA expression using quantitative polymerase chain reaction in whole blood leukocytes and protein expression in CD15 isolated neutrophils using Western blotting. Neutrophil apoptosis was assessed using the APO-BRDU method. Apolipoprotein L mRNA was downregulated in whole blood leukocytes and neutrophils in ICU patients compared with in healthy volunteers, and this effect translated at the protein level as indicated by Western blot analysis of neutrophils. There was a negative correlation between ApoL expression in neutrophils and C-reactive protein levels and a positive correlation between the number of apoptotic neutrophils and mRNA levels of ApoL1 and ApoL2. The degree of neutrophil apoptosis in critically ill patients is therefore correlated with modified expression profiles of ApoLs.
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http://dx.doi.org/10.1097/SHK.0000000000000728 | DOI Listing |
Nan Fang Yi Ke Da Xue Xue Bao
December 2024
Department of Emergency Medicine, Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University (Changsha First Hospital), Changsha 410005, China.
Objectives: To investigate the inhibitory effect of GSK484, a PAD4 inhibitor, on H3Cit expression following sepsis and its effects for improving sepsis-induced endothelial dysfunction.
Methods: Eighteen C57BL/6 mice were randomized into sham-operated group, sepsis model group and GSK484 treatment group (6), and in the latter two groups, models of sepsis were established by cecal ligation and puncture (CLP). The mice in GSK484 treatment group were given an intraperitoneal injection of GSK484 (4 mg/kg) on the second day following the surgery.
Adv Healthc Mater
December 2024
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.
During acute respiratory distress syndrome (ARDS), delayed apoptosis of neutrophils and impaired efferocytosis of macrophages constitute two critical limiting steps, leading to secondary inflammatory storm and posing a significant threat to human health. However, due to the failure of previous single target-centric treatments to effectively address these two limiting steps in controlling the inflammatory storm, no available therapies are approved for ARDS treatment. Herein, inspired by spontaneous inflammation resolution, two kinds of Apoptosis and Efferocytosis Restored Nanoparticles (AER NPs) are proposed to overcome these two limiting steps for counteracting severe inflammatory storm.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Emergency and Critical Care Medicine, Aichi Medical University, Nagakute, Japan.
Sepsis is characterized by a concomitant early pro-inflammatory response by immune cells to an infection, and an opposing anti-inflammatory response that results in protracted immunosuppression. The primary pathological event in sepsis is widespread programmed cell death, or cellular self-sacrifice, of innate and adaptive immune cells, leading to profound immunological suppression. This severe immune dysfunction hampers effective primary pathogen clearance, thereby increasing the risk of secondary opportunistic infections, latent viral reactivation, multiple organ dysfunction, and elevated mortality.
View Article and Find Full Text PDFPlacenta
December 2024
Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China; Department of Clinical Laboratory, The Laboratory of Placenta-related Diseases, Key Laboratory of Birth Regulation and Control Technology of National Health and Family Planning Commission of China, Jinan, Shandong, 250014, China. Electronic address:
Background: Inflammatory stress at the maternal-fetal interface plays an important role in the occurrence and development of preeclampsia(PE) caused by different etiologies. Many pathological neutrophil extracellular traps (NETs) at the maternal-fetal interface are believed to be among the main pathogenic factors leading to preeclampsia and the worsening of its symptoms. However, the underlying mechanism is largely unclear.
View Article and Find Full Text PDFElife
December 2024
Department of Dermatology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Psoriasis is a multifactorial immune-mediated inflammatory disease. Its pathogenesis involves abnormal accumulation of neutrophils and T-cell-related abnormalities. Pyroptosis is a type of regulated cell death associated with innate immunity, but its role in psoriasis is unclear.
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