ROS- and Radiation Source-Dependent Modulation of Leukocyte Adhesion to Primary Microvascular Endothelial Cells

Eckert, Denise; Rapp, Felicitas; Tsedeke, Ayele Taddese; Molendowska, Jessica; Lehn, Robert; Langhans, Markus; Fournier, Claudia; Rödel, Franz; Hehlgans, Stephanie

doi:10.3390/cells11010072

Cited by 15 publications

(7 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, fluid shear stress, the tangential frictional force exerted by flowing blood, also influences endothelial permeability [ 97 ]. During sepsis, decreases in blood flow velocity or changes in flow pattern are associated with decreased NO production and may exacerbate leukocyte adhesion, platelet aggregation, and inflammation [ 98 ]. Vascular endothelial growth factor (VEGF) is an important regulator of vascular permeability through the regulation of nitric oxide synthase (NOS) [ 99 ].…”

Section: Lps Deteriorates Endothelial Permeabilitymentioning

confidence: 99%

Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis

Wang,

Feng,

Zhou

et al. 2023

Eur J Med Res

View full text Add to dashboard Cite

Background Lipopolysaccharide, a highly potent endotoxin responsible for severe sepsis, is the major constituent of the outer membrane of gram-negative bacteria. Endothelial cells participate in both innate and adaptive immune responses as the first cell types to detect lipopolysaccharide or other foreign debris in the bloodstream. Endothelial cells are able to recognize the presence of LPS and recruit specific adaptor proteins to the membrane domains of TLR4, thereby initiating an intracellular signaling cascade. However, lipopolysaccharide binding to endothelial cells induces endothelial activation and even damage, manifested by the expression of proinflammatory cytokines and adhesion molecules that lead to sepsis. Main findings LPS is involved in both local and systemic inflammation, activating both innate and adaptive immunity. Translocation of lipopolysaccharide into the circulation causes endotoxemia. Endothelial dysfunction, including exaggerated inflammation, coagulopathy and vascular leakage, may play a central role in the dysregulated host response and pathogenesis of sepsis. By discussing the many strategies used to treat sepsis, this review attempts to provide an overview of how lipopolysaccharide induces the ever more complex syndrome of sepsis and the potential for the development of novel sepsis therapeutics. Conclusions To reduce patient morbidity and mortality, preservation of endothelial function would be central to the management of sepsis. Graphical Abstract

show abstract

Section: Lps Deteriorates Endothelial Permeabilitymentioning

confidence: 99%

Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis

Wang,

Feng,

Zhou

et al. 2023

Eur J Med Res

View full text Add to dashboard Cite

show abstract

“…If there are sparing dose protraction effects of low-LET radiation and enhancing protraction effects of high-LET radiation, RBE for protracted exposures can be higher than that for acute exposures, and in this regard, the impact of inverse dose protraction effects of low- and high-LET radiation needs to be considered for noncancer effects ( 95 , 104 , 157 , 157 , 186 ). Potential differences in RBE with energy of low-LET photons and electrons ( 163 , 231 , 231 , 232 ) and implications of protective effects of small dose on the circulatory system ( 233 , 234 ) would also need to be considered.…”

Section: Future Perspectivesmentioning

confidence: 99%

Noncancer Effects of Ionizing Radiation Exposure on the Eye, the Circulatory System and beyond: Developments made since the 2011 ICRP Statement on Tissue Reactions

Hamada

2023

Radiation Research

View full text Add to dashboard Cite

For radiation protection purposes, noncancer effects with a threshold-type dose-response relationship have been classified as tissue reactions (formerly called nonstochastic or deterministic effects), and equivalent dose limits aim to prevent occurrence of such tissue reactions. Accumulating evidence demonstrates increased risks for several late occurring noncancer effects at doses and dose rates much lower than previously considered. In 2011, the International Commission on Radiological Protection (ICRP) issued a statement on tissue reactions to recommend a threshold of 0.5 Gy to the lens of the eye for cataracts and to the heart and brain for diseases of the circulatory system (DCS), independent of dose rate. Literature published thereafter continues to provide updated knowledge. Increased risks for cataracts below 0.5 Gy have been reported in several cohorts (e.g., including in those receiving protracted or chronic exposures). A dose threshold for cataracts is less evident with longer follow-up, with limited evidence available for risk of cataract removal surgery. There is emerging evidence for risk of normal-tension glaucoma and diabetic retinopathy, but the long-held tenet that the lens represents among the most radiosensitive tissues in the eye and in the body seems to remain unchanged. For DCS, increased risks have been reported in various cohorts, but the existence or otherwise of a dose threshold is unclear. The level of risk is less uncertain at lower dose and lower dose rate, with the possibility that risk per unit dose is greater at lower doses and dose rates. Target organs and tissues for DCS are also unknown, but may include heart, large blood vessels and kidneys. Identification of potential factors (e.g., sex, age, lifestyle factors, coexposures, comorbidities, genetics and epigenetics) that may modify radiation risk of cataracts and DCS would be important. Other noncancer effects on the radar include neurological effects (e.g., Parkinsonŉs disease and dementia) of which elevated risk has increasingly been reported. These late occurring noncancer effects tend to deviate from the definition of tissue reactions, necessitating more scientific developments to reconsider the radiation effect classification system and risk management. This paper gives an overview of historical developments made in ICRP prior to the 2011 statement and an update on relevant developments made since the 2011 ICRP statement.

show abstract

“…[ 50 ] Once extravasated into the brain parenchyma, these peripheral immune cells initiate brain tissue damage by free‐radical reactions and NO depletion, which can cause vasoconstriction and ischemia. [ 63 , 64 ] Many physiological processes are promoted by NO. Under basal conditions, vascular ECs synthesize and release nitric oxide.…”

Section: Structural Features Of the Human Brainmentioning

confidence: 99%

“…Chronic activation of these immunocompetent cells by cytokines/chemokines further potentiates ROS production via NADPH oxidase, resulting in an inflammatory cytokine storm. [ 63 , 64 ] The result is increased activation and insult/injury to immunocompetent cells, resulting in axonal damage, neurodegeneration, and neurocognition impairments. [ 38 , 60 , 66 , 68 , 109 , 110 ]…”

Section: The Effect Of P Falciparum Infection On B...mentioning

confidence: 99%

Cerebral Malaria and Neuronal Implications ofPlasmodium FalciparumInfection: From Mechanisms to Advanced Models

2022

View full text Add to dashboard Cite

Reorganization of host red blood cells by the malaria parasite Plasmodium falciparum enables their sequestration via attachment to the microvasculature. This artificially increases the dwelling time of the infected red blood cells within inner organs such as the brain, which can lead to cerebral malaria. Cerebral malaria is the deadliest complication patients infected with P. falciparum can experience and still remains a major public health concern despite effective antimalarial therapies. Here, the current understanding of the effect of P. falciparum cytoadherence and their secreted proteins on structural features of the human blood-brain barrier and their involvement in the pathogenesis of cerebral malaria are highlighted. Advanced 2D and 3D in vitro models are further assessed to study this devastating interaction between parasite and host. A better understanding of the molecular mechanisms leading to neuronal and cognitive deficits in cerebral malaria will be pivotal in devising new strategies to treat and prevent blood-brain barrier dysfunction and subsequent neurological damage in patients with cerebral malaria. MalariaMalaria is an ancient mosquito-borne disease caused by protozoan parasites of the genus Plasmodium. According to the latest World Malaria Report published by the World Health

show abstract

ROS- and Radiation Source-Dependent Modulation of Leukocyte Adhesion to Primary Microvascular Endothelial Cells

Cited by 15 publications

References 58 publications

Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis

Bacterial lipopolysaccharide-induced endothelial activation and dysfunction: a new predictive and therapeutic paradigm for sepsis

Noncancer Effects of Ionizing Radiation Exposure on the Eye, the Circulatory System and beyond: Developments made since the 2011 ICRP Statement on Tissue Reactions

Cerebral Malaria and Neuronal Implications ofPlasmodium FalciparumInfection: From Mechanisms to Advanced Models

Contact Info

Product

Resources

About