Age-dependent Role of Microvascular Endothelial and Polymorphonuclear Cells in Lipopolysaccharide-induced Acute Kidney Injury

Wulfert, Francis M.; Meurs, Matijs van; Kurniati, Neng Fisheri; Jongman, Rianne M.; Houwertjes, M. C.; Heeringa, Peter; Struys, Michel; Zijlstra, Jan G.; Molema, Grietje

doi:10.1097/aln.0b013e31825b57c9

Cited by 22 publications

(20 citation statements)

References 44 publications

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“…In the previously mentioned studies, inhibiting TLR4 signalling or depleting leucocytes improved renal function. Other data support the opposite scenario where PMN depleted mice subjected to LPS displayed greater kidney injury compared to mice with normal PMN count (Wulfert et al 2012). Several groups have studied the significance of local renal or systemic TLR4 in leucocyte infiltration and renal dysfunction.…”

Section: Leucocyte Infiltration Tlr4 and Si-akimentioning

confidence: 94%

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Physiological aspects of Toll‐like receptor 4 activation in sepsis‐induced acute kidney injury

2016

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Sepsis‐induced acute kidney injury (SI‐AKI) is common and associated with high mortality. Survivors are at increased risk of chronic kidney disease. The precise mechanism underlying SI‐AKI is unknown, and no curative treatment exists. Toll‐like receptor 4 (TLR4) activates the innate immune system in response to exogenous microbial products. The result is an inflammatory reaction aimed at clearing a potential infection. However, the consequence may also be organ dysfunction as the immune response can cause collateral damage to host tissue. The purpose of this review is to describe the basis for how ligand binding to TLR4 has the potential to cause renal dysfunction and the mechanisms by which this may take place in gram‐negative sepsis. In addition, we highlight areas for future research that can further our knowledge of the pathogenesis of SI‐AKI in relation to TLR4 activation. TLR4 is expressed in the kidney. Activation of TLR4 causes cytokine and chemokine release as well as renal leucocyte infiltration. It also results in endothelial and tubular dysfunction in addition to altered renal metabolism and circulation. From a physiological standpoint, inhibiting TLR4 in large animal experimental SI‐AKI significantly improves renal function. Thus, current evidence indicates that TLR4 has the ability to mediate SI‐AKI by a number of mechanisms. The strong experimental evidence supporting a role of TLR4 in the pathogenesis of SI‐AKI in combination with the availability of pharmacological tools to target TLR4 warrants future human studies.

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Section: Leucocyte Infiltration Tlr4 and Si-akimentioning

confidence: 94%

“…Other data support the opposite scenario where PMN depleted mice subjected to LPS displayed greater kidney injury compared to mice with normal PMN count (Wulfert et al . ).…”

Section: Leucocyte Infiltration Tlr4 and Si‐akimentioning

confidence: 97%

Physiological aspects of Toll‐like receptor 4 activation in sepsis‐induced acute kidney injury

2016

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“…In addition to changes in their life span, neutrophil recruitment is altered with advanced age and after alcohol consumption. Some groups have reported that, with advanced age, neutrophil recruitment to the site of inflammation or infection was reduced or delayed, which was not due to lessened neutrophil chemoattractant levels [102][103][104][105][106][107]; yet, other studies showed heightened neutrophil recruitment in aged mice compared with young mice, possibly because of higher levels of cellular-adhesion molecules present on the endothelial cells that neutrophils transverse to migrate from the circulation into tissues [108][109][110][111]. The directed migration of neutrophils is compromised with advanced age both in vitro and in vivo, likely because of perturbations in signal transduction [104,112].…”

Section: Neutrophilsmentioning

confidence: 99%

Alcohol, aging, and innate immunity

Boule

Kovacs

2017

Journal of Leukocyte Biology

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The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption. In fact, it has been estimated that >40% of older adults consume alcohol, and evidence reveals that >10% of this group is drinking more than the recommended limit by the National Institute on Alcohol Abuse and Alcoholism. Alcohol consumption, at any level, alters host immune responses, including changes in the number, phenotype, and function of innate and adaptive immune cells. Thus, understanding the effect of alcohol ingestion on the immune system of older individuals, who are already less capable of combating infection, merits further study. However, there is currently almost nothing known about how drinking alters innate immunity in older subjects, despite innate immune cells being critical for host defense, resolution of inflammation, and maintenance of immune homeostasis. Here, we review the effects of aging and alcohol consumption on innate immune cells independently and highlight the few studies that have examined the effects of alcohol ingestion in aged individuals.

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“…Endothelial activation can be represented by elevated levels of circulating sE-selectin, sVCAM-1, and sICAM-1 in the blood of patients with sepsis (6) and after CPB (7Y10). The proinflammatory endothelial activation leads to recruitment of polymorphonuclear leukocytes (PMNs) into organs (11), where they become activated and release cytotoxic enzymes, including elastase and myeloperoxidase (MPO). Elevated levels of these enzymes in the blood indicate that the use of CPB during CABG results in activation of PMNs (12).…”

Section: Introductionmentioning

confidence: 99%

Off-Pump CABG Surgery Reduces Systemic Inflammation Compared With On-Pump Surgery but Does Not Change Systemic Endothelial Responses

Jongman

Zijlstra²,

Kok³

et al. 2014

Shock

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Coronary artery bypass graft (CABG) surgery can result in severe postoperative organ failure. During CABG surgery, cardiopulmonary bypass (CPB) with cardiac arrest is often used (on-pump CABG), which often results in a systemic inflammatory response. To reduce this inflammatory response, off-pump CABG was reintroduced, thereby avoiding CPB. There is increasing evidence that the endothelium plays an important role in the pathophysiology of organ failure after CABG surgery. In this study, 60 patients who were scheduled for elective CABG surgery were randomized to have surgery for on-pump or off-pump CABG. Blood was collected at four time points: start, end, 6 h, and 24 h postoperatively. Levels of inflammatory cytokines, soluble adhesion molecules, and angiogenic factors and their receptors were measured in the plasma. No differences were found in preoperative characteristics between the patient groups. The levels of tumor necrosis factor-α, interleukin 10, and myeloperoxidase, but not interleukin 6, were increased to a greater extent in the on-pump CABG compared with off-pump CABG after sternum closure. The soluble endothelial adhesion molecules E-selectin, vascular cell adhesion molecule 1, and intracellular adhesion molecule 1 were not elevated in the plasma during and after CABG surgery in both on-pump and off-pump CABG. Angiopoietin 2 was only increased 24 h after surgery in both on-pump and off-pump CABG. Higher levels of sFlt-1 were found after sternum closure in off-pump CABG compared with on-pump CABG. Avoiding CPB and aortic cross clamping in CABG surgery reduces the systemic inflammatory response. On-pump CABG does not lead to an increased release of soluble endothelial adhesion molecules in the circulation compared with off-pump CABG.

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Age-dependent Role of Microvascular Endothelial and Polymorphonuclear Cells in Lipopolysaccharide-induced Acute Kidney Injury

Abstract: Ang-2 is increased in older mice, which might cause priming of the endothelial cells. Endothelium responded by a more extensive increase in expression of P- and E-selectin in older mice and increased polymorphonuclear cell influx.

Cited by 22 publications

References 44 publications

Physiological aspects of Toll‐like receptor 4 activation in sepsis‐induced acute kidney injury

Physiological aspects of Toll‐like receptor 4 activation in sepsis‐induced acute kidney injury

Alcohol, aging, and innate immunity

Off-Pump CABG Surgery Reduces Systemic Inflammation Compared With On-Pump Surgery but Does Not Change Systemic Endothelial Responses

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