Interaction between Erythropoietin and Peripheral Polymorphonuclear Leukocytes in Hemodialysis Patients

Kristal, Batya; Shurtz-Swirski, Revital; Shasha, Shaul M.; Manaster, J.; Shapiro, Galina; Furmanov, Michael; Hassan, Kamal; Weissman, Irith; Sela, Shifra

doi:10.1159/000045324

Cited by 40 publications

(41 citation statements)

References 29 publications

(34 reference statements)

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“…reported that PMNL from patients with chronic kidney disease (CKD) both before and while on renal replacement therapy (RRT) are primed. Our studies have also shown that PMNL are in a primed state in both continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) patients (7,8). In addition to CKD patients, we have shown PMNL priming as a common denominator in other clinical states, such as hypertension, diabetes, and cigarette smoking, that are known to be associated with endothelial dysfunction, accelerated atherosclerosis, and increased prevalence of cardiovascular morbidity and mortality (9 -11).…”

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confidence: 88%

“…In addition to CKD patients, we have shown PMNL priming as a common denominator in other clinical states, such as hypertension, diabetes, and cigarette smoking, that are known to be associated with endothelial dysfunction, accelerated atherosclerosis, and increased prevalence of cardiovascular morbidity and mortality (9 -11). In all of these clinical states, it was apparent that primed peripheral PMNL contribute concomitantly to chronic systemic oxidative stress (OS) and inflammatory processes and that PMNL priming was associated with a significant increase in peripheral white blood cells (WBC) and PMNL counts, although still in the upper quadrant of the normal range (7)(8)(9)(10)(11). Recently, epidemiologic studies have suggested that elevated WBC and neutrophil counts constitute a mortality predictor in HD patients (12,13) and are a risk factor for developing CKD in U.S. adults (14).…”

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confidence: 99%

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Primed Peripheral Polymorphonuclear Leukocyte

Sela¹,

Shurtz-Swirski²,

Cohen-Mazor³

et al. 2005

Journal of the American Society of Nephrology

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171

126

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This study characterizes the causal relationship between peripheral polymorphonuclear leukocyte (PMNL) priming, systemic oxidative stress (OS), and inflammation in patients with varying degrees of renal insufficiency (chronic kidney disease [CKD] not on renal replacement therapy [RRT]: continuous ambulatory peritoneal dialysis or hemodialysis [HD]) and healthy control subjects. Rate of superoxide release was measured after stimulation of PMNL with phorbol 12-myristate 13-acetate or zymosan. Priming was estimated by the rate of superoxide release after phorbol 12-myristate 13-acetate stimulation. Systemic OS was related to PMNL priming and intracellular myeloperoxidase activity. Inflammation was linked to peripheral white blood cells and PMNL counts, PMNL apoptosis, and PMNL ex vivo survival in autologous and heterologous sera. PMNL priming and counts were related to the severity of renal failure in CKD not on RRT. Compared with control subjects, PMNL from all CKD patients showed increased priming, highest in HD, with a significant decrease in their response to zymosan. PMNL myeloperoxidase activity and apoptosis were increased in all renal failure patients. Decreased ex vivo cell survival and elevated leukocyte counts were found in all patients, highest in HD. Both PMNL priming and counts correlated negatively with the GFR. A positive significant correlation was shown between PMNL counts and their priming in all groups, suggesting that the increased PMNL count in peripheral blood is an adaptive response to PMNL priming. Hence, PMNL priming is a key mediator of low-grade inflammation and OS associated with renal failure, occurring before the onset of RRT and further augmented in chronic HD.

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confidence: 88%

mentioning

confidence: 99%

Primed Peripheral Polymorphonuclear Leukocyte

Sela¹,

Shurtz-Swirski²,

Cohen-Mazor³

et al. 2005

Journal of the American Society of Nephrology

Self Cite

171

126

View full text Add to dashboard Cite

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“…Results from in vivo studies using experimental models of global and focal ischemia, blunt trauma, immune-mediated inflammation, excitotoxin-elicited seizures, subarachnoidal hemorrhage, and toxininduced Parkinsonism suggest that EPO might be a beneficial agent in these situations (4-6, 9, 11-13). Although the exact mechanism of the EPO's neuroprotective effect is not fully known, promotion of cell survival signaling cascades (7,(14)(15)(16), attenuation of intracellular calcium and nitric oxide production (13,17,18), and antioxidative (19,20) and anti-inflammatory actions (5, 7) have been implicated as possible mechanisms.…”

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confidence: 99%

Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury

Çeli̇k

Gökmen

Erbayraktar

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

433

275

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The cytokine erythropoietin (EPO) possesses potent neuroprotective activity against a variety of potential brain injuries, including transient ischemia and reperfusion. It is currently unknown whether EPO will also ameliorate spinal cord injury. Immunocytochemistry performed using human spinal cord sections showed abundant EPO receptor immunoreactivity of capillaries, especially in white matter, and motor neurons within the ventral horn. We used a transient global spinal ischemia model in rabbits to test whether exogenous EPO can cross the blood-spinal cord barrier and protect these motor neurons. Spinal cord ischemia was produced in rabbits by occlusion of the abdominal aorta for 20 min, followed by saline or recombinant human (rHu)-EPO (350, 800, or 1,000 units/kg of body weight) administered intravenously immediately after the onset of reperfusion. The functional neurological status of animals was better for rHu-EPO-treated animals 1 h after recovery from anesthesia, and improved dramatically over the next 48 h. In contrast, saline-treated animals exhibited a poorer neurological score at 1 h and did not significantly improve. Histopathological examination of the affected spinal cord revealed widespread motor neuron injury associated with positive terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling in control but not in rHu-EPO-treated animals. These observations suggest both an acute as well as a delayed beneficial action of rHu-EPO in ischemic spinal cord injury. Because rHu-EPO is currently used widely with an excellent safety profile, clinical trials evaluating its potential to prevent motor neuron apoptosis and the neurological deficits that occur as a consequence of ischemic injury are warranted.

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“…Kristal et al [35] showed that there is a strong positive correlation between the percentage of EPOR-positive cells and the level of EPO in the serum which suggested that presence of hormone upregulates the expression of receptor. Moreover, following few weeks of rhEPO treatment, in HD patients, the rate of superoxide release from granulocytes fell significantly when compared with the pretreatment values.…”

Section: Role Of Erythropoietin and Its Recep-tor In Modulating Immunmentioning

confidence: 99%

The Role of Erythropoietin and its Receptor in the Immune, Central Nervous and Cardiovascular Systems

Lisowska

2015

International Journal of Hematology Research

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Primary role of erythropoietin (EPO) is to protect red blood cell progenitors from apoptosis and to stimulate their growth and differentiation by binding to its receptor (EPOR). However, the expression of EPOR has been identified on other human cells, such as granulocytes, monocytes, lymphocytes, endothelial cells and neurons. Its presence on these cells suggests that beyond erythropoietic function EPO might have some other properties. Various studies show that recombinant human erythropoietin (rhEPO) used in the treatment of anemia associated with chronic kidney disease (CKD) has potentially beneficial influence on cellular processes such as proliferation and apoptosis of cells other than erythrocyte progenitors. It can modulate the activity of immune cells, protect neurons from apoptosis and even stimulate angiogenesis, but also it has a prothrombotic properties. This review presents current knowledge on the role of EPO and its receptor in the immune, central nervous and cardiovascular systems in various pathophysiological situations.

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Interaction between Erythropoietin and Peripheral Polymorphonuclear Leukocytes in Hemodialysis Patients

Cited by 40 publications

References 29 publications

Primed Peripheral Polymorphonuclear Leukocyte

Primed Peripheral Polymorphonuclear Leukocyte

Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury

The Role of Erythropoietin and its Receptor in the Immune, Central Nervous and Cardiovascular Systems

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