This page has only limited features, please log in for full access.
In uremic patients, high-density lipoprotein (HDL) loses its anti-inflammatory features and can even become pro-inflammatory due to an altered protein composition. In chronic kidney disease (CKD), impaired functions of polymorphonuclear leukocytes (PMNLs) contribute to inflammation and an increased risk of cardiovascular disease. This study investigated the effect of HDL from CKD and hemodialysis (HD) patients on the CD14 expression on PMNLs. HDL was isolated using a one-step density gradient centrifugation. Isolation of PMNLs was carried out by discontinuous Ficoll-Hypaque density gradient centrifugation. CD14 surface expression was quantified by flow cytometry. The activity of the small GTPase Rac1 was determined by means of an activation pull-down assay. HDL increased the CD14 surface expression on PMNLs. This effect was more pronounced for HDL isolated from uremic patients. The acute phase protein serum amyloid A (SAA) caused higher CD14 expression, while SAA as part of an HDL particle did not. Lipid raft disruption with methyl-β-cyclodextrin led to a reduced CD14 expression in the absence and presence of HDL. HDL from healthy subjects but not from HD patients decreased the activity of Rac1. Considering the known anti-inflammatory effects of HDL, the finding that even HDL from healthy subjects increased the CD14 expression was unexpected. The pathophysiological relevance of this result needs further investigation.
Gerald Cohen. Effect of High-Density Lipoprotein from Healthy Subjects and Chronic Kidney Disease Patients on the CD14 Expression on Polymorphonuclear Leukocytes. International Journal of Molecular Sciences 2021, 22, 2830 .
AMA StyleGerald Cohen. Effect of High-Density Lipoprotein from Healthy Subjects and Chronic Kidney Disease Patients on the CD14 Expression on Polymorphonuclear Leukocytes. International Journal of Molecular Sciences. 2021; 22 (6):2830.
Chicago/Turabian StyleGerald Cohen. 2021. "Effect of High-Density Lipoprotein from Healthy Subjects and Chronic Kidney Disease Patients on the CD14 Expression on Polymorphonuclear Leukocytes." International Journal of Molecular Sciences 22, no. 6: 2830.
This Special Issue of Toxins focusses on the interconnected factors interfering with the immune response in uremic patients
Gerald Cohen; Raymond Vanholder. Special Issue: Immune Dysfunction in Uremia. Toxins 2021, 13, 70 .
AMA StyleGerald Cohen, Raymond Vanholder. Special Issue: Immune Dysfunction in Uremia. Toxins. 2021; 13 (1):70.
Chicago/Turabian StyleGerald Cohen; Raymond Vanholder. 2021. "Special Issue: Immune Dysfunction in Uremia." Toxins 13, no. 1: 70.
Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failure results in disturbed renal metabolic activities with reduced renin, erythropoietin, and vitamin D production, which adversely affects the immune system. Decreased kidney function also leads to reduced glomerular filtration and the retention of uremic toxins. A large number of uremic toxins with detrimental effects on immune cells have been identified. Besides small water-soluble and protein-bound compounds originating from the intestinal microbiome, several molecules in the middle molecular range, e.g., immunoglobulin light chains, retinol-binding protein, the neuropeptides Met-enkephalin and neuropeptide Y, endothelin-1, and the adipokines leptin and resistin, adversely affect immune cells. Posttranslational modifications such as carbamoylation, advanced glycation products, and oxidative modifications contribute to uremic toxicity. Furthermore, high-density lipoprotein from uremic patients has an altered protein profile and thereby loses its anti-inflammatory properties.
Gerald Cohen. Immune Dysfunction in Uremia 2020. Toxins 2020, 12, 439 .
AMA StyleGerald Cohen. Immune Dysfunction in Uremia 2020. Toxins. 2020; 12 (7):439.
Chicago/Turabian StyleGerald Cohen. 2020. "Immune Dysfunction in Uremia 2020." Toxins 12, no. 7: 439.
The anti-inflammatory properties of high-density lipoproteins (HDL) are lost in uremia. These HDL may show pro-inflammatory features partially as a result of changed protein composition. Alterations of polymorphonuclear leukocytes (PMNLs) in chronic kidney disease (CKD) may contribute to chronic inflammation and high vascular risk. We investigated if HDL from uremic patients is related to systemic inflammation by interfering with PMNL function. PMNL apoptosis was investigated by assessing morphological features and DNA content. CD11b surface expression was quantified by flow cytometry. Oxidative burst was measured via cytochrome c reduction assay. Chemotaxis was assessed by using an under-agarose migration assay. We found that HDL from CKD and hemodialysis (HD) patients significantly attenuated PMNL apoptosis, whereas HDL isolated from healthy subjects had no effect on PMNL apoptosis. The use of signal transduction inhibitors indicated that uremic HDL exerts anti-apoptotic effects by activating pathways involving phosphoinositide 3-kinase and extracellular-signal regulated kinase. Healthy HDL attenuated the surface expression of CD11b, whereas HDL from CKD and HD patients had no effect. All tested isolates increased the stimulation of oxidative burst, but did not affect PMNL chemotactic movement. In conclusion, HDL may contribute to the systemic inflammation in uremic patients by modulating PMNL functions.
Jana Raupachova; Chantal Kopecky; Gerald Cohen. High-Density Lipoprotein from Chronic Kidney Disease Patients Modulates Polymorphonuclear Leukocytes. Toxins 2019, 11, 73 .
AMA StyleJana Raupachova, Chantal Kopecky, Gerald Cohen. High-Density Lipoprotein from Chronic Kidney Disease Patients Modulates Polymorphonuclear Leukocytes. Toxins. 2019; 11 (2):73.
Chicago/Turabian StyleJana Raupachova; Chantal Kopecky; Gerald Cohen. 2019. "High-Density Lipoprotein from Chronic Kidney Disease Patients Modulates Polymorphonuclear Leukocytes." Toxins 11, no. 2: 73.
Gerald Cohen; Jana Raupachova; Kyra Borchhardt; Walter H. Hörl. Cinacalcet effect on polymorphonuclear leucocytes of kidney transplant patients. European Journal of Clinical Investigation 2013, 43, 476 -482.
AMA StyleGerald Cohen, Jana Raupachova, Kyra Borchhardt, Walter H. Hörl. Cinacalcet effect on polymorphonuclear leucocytes of kidney transplant patients. European Journal of Clinical Investigation. 2013; 43 (5):476-482.
Chicago/Turabian StyleGerald Cohen; Jana Raupachova; Kyra Borchhardt; Walter H. Hörl. 2013. "Cinacalcet effect on polymorphonuclear leucocytes of kidney transplant patients." European Journal of Clinical Investigation 43, no. 5: 476-482.
The activation of polymorphonuclear leucocytes (PMNLs) causes inflammation and as a result cardiovascular disease, which is a main risk factor for increased morbidity and mortality in patients with chronic kidney disease. Toxins accumulating in uraemic patients play a major role in modulating essential PMNL functions and apoptosis, the latter being crucial for a coordinated resolution of inflammation. One uraemic toxin is phenylacetic acid (PAA). We therefore investigated whether PAA contributes to the deranged immune response in uraemia by modulating PMNL activities. PMNL oxidative burst, phagocytosis and surface expression of the activation markers CD11b and CD18 were measured by flow cytometry in whole blood from healthy subjects in the presence and absence of PAA. Spontaneous apoptosis of isolated PMNLs was assessed by evaluating morphological features under the fluorescence microscope and by measuring the DNA content by flow cytometry. PMNL chemotaxis was tested by the under-agarose method. PAA significantly enhanced the stimulation of PMNL oxidative burst by Escherichia coli, phagocytosis of E. coli by PMNLs and the expression of CD11b and CD18 at the PMNL surface. PAA significantly decreased PMNL apoptosis resulting in an increased percentage of viable cells. PAA affected neither the oxidative burst stimulated by phorbol-12-myristate-13-acetate nor PMNL chemotaxis. PAA increases the activation of various PMNL functions and the expression of surface activation markers, while it attenuates PMNL apoptotic cell death. Therefore, PAA may contribute to the inflammatory state and consequently to increased cardiovascular risk in uraemic patients.
Gerald Cohen; Jana Raupachova; Walter H. Hörl. The uraemic toxin phenylacetic acid contributes to inflammation by priming polymorphonuclear leucocytes. Nephrology Dialysis Transplantation 2012, 28, 421 -429.
AMA StyleGerald Cohen, Jana Raupachova, Walter H. Hörl. The uraemic toxin phenylacetic acid contributes to inflammation by priming polymorphonuclear leucocytes. Nephrology Dialysis Transplantation. 2012; 28 (2):421-429.
Chicago/Turabian StyleGerald Cohen; Jana Raupachova; Walter H. Hörl. 2012. "The uraemic toxin phenylacetic acid contributes to inflammation by priming polymorphonuclear leucocytes." Nephrology Dialysis Transplantation 28, no. 2: 421-429.
Kidney dysfunction leads to disturbed renal metabolic activities and to impaired glomerular filtration, resulting in the retention of toxic solutes affecting all organs of the body. Cardiovascular disease (CVD) and infections are the main causes for the increased occurrence of morbidity and mortality among patients with chronic kidney disease (CKD). Both complications are directly or indirectly linked to a compromised immune defense. The specific coordinated roles of polymorphonuclear leukocytes (PMNLs), monocytes/macrophages, lymphocytes and antigen-presenting cells (APCs) in maintaining an efficient immune response are affected. Their normal response can be impaired, giving rise to infectious diseases or pre-activated/primed, leading to inflammation and consequently to CVD. Whereas the coordinated removal via apoptosis of activated immune cells is crucial for the resolution of inflammation, inappropriately high apoptotic rates lead to a diminished immune response. In uremia, the balance between pro- and anti-inflammatory and between pro- and anti-apoptotic factors is disturbed. This review summarizes the interrelated parameters interfering with the immune response in uremia, with a special focus on the non-specific immune response and the role of uremic toxins.
Gerald Cohen; Walter H. Hörl. Immune Dysfunction in Uremia—An Update. Toxins 2012, 4, 962 -990.
AMA StyleGerald Cohen, Walter H. Hörl. Immune Dysfunction in Uremia—An Update. Toxins. 2012; 4 (11):962-990.
Chicago/Turabian StyleGerald Cohen; Walter H. Hörl. 2012. "Immune Dysfunction in Uremia—An Update." Toxins 4, no. 11: 962-990.
Background. Dysfunction of polymorphonuclear leucocytes (PMNLs) in end-stage renal disease (ESRD) patients contributes to a diminished immune defence. The serum levels of leptin are elevated in patients with ESRD. We analysed in vitro effects of leptin on PMNLs from healthy subjects (HS; n = 12) and haemodialysis (HD) patients (n = 15) before and after HD. Methods. PMNL oxidative burst and phagocytosis were tested by flow cytometry in whole blood. Chemotaxis of isolated PMNLs was assessed by the under-agarose method. To assess the involvement of leptin in PMNL signalling pathways, signal transduction inhibitors were used and the activity of intracellular kinases was investigated by western blotting, in vitro kinase assays and the Luminex technology. Results. Increasing the leptin level in the blood of HS leads to a reduced activation of the oxidative burst by Escherichia coli and phorbol 12-myristate 13-acetate. Activation of the oxidative burst is reduced in the blood of HD patients and the addition of leptin does not lead to further PMNL inhibition. Leptin at a concentration measured in HD patients significantly reduces the chemotaxis of PMNLs from HS but had no effect on PMNLs from ESRD patients before and also after HD treatment with high-flux dialysers. The phosphoinositide 3-kinase/Akt pathway is involved in the inhibitory effects of leptin. Conclusions. In the presence of leptin, PMNLs from HS and HD patients respond differently to stimuli. The lack of response to leptin in PMNLs from HD patients cannot be influenced by HD.
Gerald Cohen; Jana Raupachova; Dalibor Ilic; Johannes Werzowa; Walter H. Hörl. Effect of leptin on polymorphonuclear leucocyte functions in healthy subjects and haemodialysis patients. Nephrology Dialysis Transplantation 2011, 26, 2271 -2281.
AMA StyleGerald Cohen, Jana Raupachova, Dalibor Ilic, Johannes Werzowa, Walter H. Hörl. Effect of leptin on polymorphonuclear leucocyte functions in healthy subjects and haemodialysis patients. Nephrology Dialysis Transplantation. 2011; 26 (7):2271-2281.
Chicago/Turabian StyleGerald Cohen; Jana Raupachova; Dalibor Ilic; Johannes Werzowa; Walter H. Hörl. 2011. "Effect of leptin on polymorphonuclear leucocyte functions in healthy subjects and haemodialysis patients." Nephrology Dialysis Transplantation 26, no. 7: 2271-2281.
Immunoglobulin light chains (IgLCs) are part of intact immunoglobulins and contribute to antigen recognition. However, IgLCs are synthesized by B cells slightly in excess of Ig heavy chains and are found in the plasma of healthy people at low concentrations. IgLCs are metabolized primarily by the kidney. In B-cell lymphoproliferative disorders, e.g., multiple myeloma, the serum concentration of monoclonal IgLCs markedly increases and the reabsorptive capacity of the proximal tubuli is exceeded. As a consequence, monoclonal IgLCs appear as Bence Jones proteins (BJPs) in the urine and can give rise to IgLC deposits in the kidney that may result in renal insufficiency. In patients with chronic kidney disease (CKD) of various origins, reduced excretion leads to increased serum levels of polyclonal IgLCs. Free IgLCs interfere with essential functions of neutrophils, cells of the first-line nonspecific immune defense, and therefore contribute to the disturbed immune function in CKD patients. IgLCs attenuate the coordinated apoptotic cell death of neutrophils and therefore may interfere with the normal resolution of inflammation and contribute to the chronic inflammatory state found in CKD patients. Recently it was shown that IgLCs may confer mast cell-dependent hypersensitivity and thereby play an important role in the development of contact sensitivity.
Gerald Cohen; Walter H. Hörl. Free Immunoglobulin Light Chains as a Risk Factor in Renal and Extrarenal Complications. Seminars in Dialysis 2009, 22, 369 -372.
AMA StyleGerald Cohen, Walter H. Hörl. Free Immunoglobulin Light Chains as a Risk Factor in Renal and Extrarenal Complications. Seminars in Dialysis. 2009; 22 (4):369-372.
Chicago/Turabian StyleGerald Cohen; Walter H. Hörl. 2009. "Free Immunoglobulin Light Chains as a Risk Factor in Renal and Extrarenal Complications." Seminars in Dialysis 22, no. 4: 369-372.
Resistin is a 12.5 kDa protein originally found to be secreted by mouse adipocytes. Whereas in rodents adipose tissue is the main source of resistin, in humans resistin is expressed primarily in macrophages. In a variety of pathophysiologic states, particularly in type 2 diabetes mellitus and in chronic kidney disease, the serum concentration of resistin is increased. Resistin reduces the glucose uptake in adipose tissue and skeletal muscle cells and may be involved in insulin resistance. A positive correlation between resistin levels and inflammatory markers has been described. Resistin has a potential role in cardiovascular disease and may contribute to an increased atherosclerotic risk by modulating the activity of endothelial cells. We recently found that resistin in concentrations measured in uremia is able to interfere with the chemotactic movement and the oxidative burst of neutrophils, cells of the first-line nonspecific immune defense. Therefore, resistin may also contribute to the disturbed immune response and as a consequence to the increased risk of infections in uremic and diabetic subjects.
Gerald Cohen; Walter H. Hörl. Resistin as a Cardiovascular and Atherosclerotic Risk Factor and Uremic Toxin. Seminars in Dialysis 2009, 22, 373 -377.
AMA StyleGerald Cohen, Walter H. Hörl. Resistin as a Cardiovascular and Atherosclerotic Risk Factor and Uremic Toxin. Seminars in Dialysis. 2009; 22 (4):373-377.
Chicago/Turabian StyleGerald Cohen; Walter H. Hörl. 2009. "Resistin as a Cardiovascular and Atherosclerotic Risk Factor and Uremic Toxin." Seminars in Dialysis 22, no. 4: 373-377.
Background. Disturbed polymorphonuclear leukocyte (PMNL) apoptosis contributes to the dysregulation of the non-specific immune system in uraemia. Intracellular Ca 2+ modulates PMNL apoptotic cell death. We investigated the effect of para -hydroxy-hippuric acid (PHA), an erythrocyte plasma membrane Ca 2+ -ATPase inhibitor accumulating in uraemic sera, and of cyclopiazonic acid (CPA), an inhibitor of the sarko/endoplasmatic Ca 2+ -ATPase, on PMNL apoptosis. Methods. Apoptosis of PMNLs from healthy subjects and from haemodialysis (HD) patients was assessed after incubation for 20 h by evaluating morphological features under the fluorescence microscope and by measuring the DNA content and caspase activities by flow cytometry. The intracellular calcium concentration ([Ca 2+ ] i ) was determined by measurement of fura-2 fluorescence using the 340/ 380 nm dual wavelength excitation. Results. Spontaneous apoptosis of PMNLs from healthy subjects and from HD patients did not differ. PHA significantly attenuated, while CPA increased, the apoptotic cell death of PMNLs from healthy subjects. The PHA effect was not observed with PMNLs from HD patients, irrespective of whether the blood was drawn before or after HD treatment. Baseline [Ca 2+ ] i was increased in PMNLs obtained from HD patients before dialysis but reversed after dialysis. The PHA effects were not mediated via [Ca 2+ ] i . The chemotactic peptide N -formyl- l -methionyl- l -leucyl- l -phenylalanine (fMLP) induced a [Ca 2+ ] i increase and reduced PMNL survival. Extracellular Ca 2+ did not affect CPA- and fMLP-induced apoptosis. Conclusions. PHA, without affecting [Ca 2+ ] i , attenuates apoptosis of healthy but not of uraemic PMNLs. CPA and fMLP enhance PMNL apoptosis independently of Ca 2+ influx.
Gerald Cohen; Jana Raupachova; Thomas Wimmer; Robert Deicher; Walter H. Hörl. The uraemic retention solute para-hydroxy-hippuric acid attenuates apoptosis of polymorphonuclear leukocytes from healthy subjects but not from haemodialysis patients. Nephrology Dialysis Transplantation 2008, 23, 2512 -2519.
AMA StyleGerald Cohen, Jana Raupachova, Thomas Wimmer, Robert Deicher, Walter H. Hörl. The uraemic retention solute para-hydroxy-hippuric acid attenuates apoptosis of polymorphonuclear leukocytes from healthy subjects but not from haemodialysis patients. Nephrology Dialysis Transplantation. 2008; 23 (8):2512-2519.
Chicago/Turabian StyleGerald Cohen; Jana Raupachova; Thomas Wimmer; Robert Deicher; Walter H. Hörl. 2008. "The uraemic retention solute para-hydroxy-hippuric acid attenuates apoptosis of polymorphonuclear leukocytes from healthy subjects but not from haemodialysis patients." Nephrology Dialysis Transplantation 23, no. 8: 2512-2519.
The progression of chronic kidney disease (CKD) leads to the dysfunction of multiple organs with clinical features constituting the uraemic syndrome and is characterized by a variety of metabolic and enzymatic disturbances. Many different substances, which are normally secreted into the urine by the healthy kidneys, are retained in the body. Those uraemic retention solutes which are the main actors during the development and manifestation of the uraemic syndrome are called uraemic toxins [ 1 ]. The identification, characterization and analytical determination of toxins responsible for the adverse biological effects encountered in uraemia and the knowledge of their patho-physiological importance is crucial for future prevention and therapy in patients with CKD stage 5. The information obtained from these analyses will make it possible to evaluate existing therapeutic approaches and to define new prognostic markers for the removal of uraemic toxins and, more importantly, it will allow the design of new specific removal strategies or other interventions to decrease and even normalize the plasma levels of uraemic toxins.
Gerald Cohen; Griet Glorieux; Paul Thornalley; Eva Schepers; Natalie Meert; Joachim Jankowski; Vera Jankowski; Angel Argiles; Björn Anderstam; Philippe Brunet; Claire Cerini; Laetitia Dou; Reinhold Deppisch; Bart Marescau; Ziad Massy; Alessandra Perna; Jana Raupachova; Mariano Rodriguez; Bernd Stegmayr; Raymond Vanholder; Walter H. Hörl; for the European Uremic Toxin Work Group (EUTox). Review on uraemic toxins III: recommendations for handling uraemic retention solutes in vitro towards a standardized approach for research on uraemia. Nephrology Dialysis Transplantation 2007, 22, 3381 -3390.
AMA StyleGerald Cohen, Griet Glorieux, Paul Thornalley, Eva Schepers, Natalie Meert, Joachim Jankowski, Vera Jankowski, Angel Argiles, Björn Anderstam, Philippe Brunet, Claire Cerini, Laetitia Dou, Reinhold Deppisch, Bart Marescau, Ziad Massy, Alessandra Perna, Jana Raupachova, Mariano Rodriguez, Bernd Stegmayr, Raymond Vanholder, Walter H. Hörl, for the European Uremic Toxin Work Group (EUTox). Review on uraemic toxins III: recommendations for handling uraemic retention solutes in vitro towards a standardized approach for research on uraemia. Nephrology Dialysis Transplantation. 2007; 22 (12):3381-3390.
Chicago/Turabian StyleGerald Cohen; Griet Glorieux; Paul Thornalley; Eva Schepers; Natalie Meert; Joachim Jankowski; Vera Jankowski; Angel Argiles; Björn Anderstam; Philippe Brunet; Claire Cerini; Laetitia Dou; Reinhold Deppisch; Bart Marescau; Ziad Massy; Alessandra Perna; Jana Raupachova; Mariano Rodriguez; Bernd Stegmayr; Raymond Vanholder; Walter H. Hörl; for the European Uremic Toxin Work Group (EUTox). 2007. "Review on uraemic toxins III: recommendations for handling uraemic retention solutes in vitro towards a standardized approach for research on uraemia." Nephrology Dialysis Transplantation 22, no. 12: 3381-3390.
Protein factors accumulating in sera of patients with end-stage renal disease (ESRD) that interfere with the nonspecific immune response by inhibiting essential functions of polymorphonuclear leucocytes (PMNLs) have previously been described. No such factor has been isolated from acute renal failure (ARF) patients to date. Using a three-step chromatographic procedure involving ion exchange, size exclusion and hydrophobic interaction chromatography we purified the apo- and holo-form of retinol binding protein (RBP) from high-flux dialyser (polyacrylonitrile; AN69) ultrafiltrates of patients with ARF. Their effect on the chemotaxis of PMNLs isolated from healthy donors was determined by the under-agarose method. Whole-blood assays applying flow cytometry were used to assess phagocytosis and the oxidative metabolism of PMNLs. Apoptosis was assessed by determining the DNA content using propidium iodide. Isolated apo- and holo-forms of RBP were truncated on their C-terminus as determined by mass spectrometry. All isolates significantly inhibited the chemotactic movement of PMNLs obtained from healthy donors and the PMNL oxidative metabolism stimulated by E. coli. These effects were concentration dependent. Retinol binding protein had no influence on the PMNL oxidative metabolism stimulated by PMA and on PMNL phagocytosis. Commercially available RBP isolated from urine influenced PMNL functions in the same way. Inhibition of p38 mitogen-activated protein kinase (MAPK) by SB203580 significantly attenuated the phagocytosis-induced respiratory burst and RBP did not lead to a further decrease. Polymorphonuclear leucocyte apoptosis was significantly inhibited by RBP. The apo- and holo-forms of RBP isolated from the ultrafiltrate of ARF patients inhibit PMNL chemotaxis, oxidative metabolism and apoptosis. Therefore, RBP may be considered a uraemic toxin contributing to a disturbed immune defence.
G. Cohen; W. H. Hörl. Retinol binding protein isolated from acute renal failure patients inhibits polymorphonuclear leucocyte functions. European Journal of Clinical Investigation 2004, 34, 774 -781.
AMA StyleG. Cohen, W. H. Hörl. Retinol binding protein isolated from acute renal failure patients inhibits polymorphonuclear leucocyte functions. European Journal of Clinical Investigation. 2004; 34 (11):774-781.
Chicago/Turabian StyleG. Cohen; W. H. Hörl. 2004. "Retinol binding protein isolated from acute renal failure patients inhibits polymorphonuclear leucocyte functions." European Journal of Clinical Investigation 34, no. 11: 774-781.
Background. Tamm–Horsfall protein (THP), a glycoprotein produced exclusively by renal tubular cells, is thought to be involved in several inflammatory disorders such as bacterial interstitial nephritis as well as in defence against uropathogenic microorganisms. The specific effects of THP on inflammatory cells, however, are not yet well known. Therefore, the present study investigates the effects of THP in its soluble form on distinct polymorphonuclear leukocyte (PMNL) functions. Methods. PMNL were isolated from the venous blood of healthy adult donors and incubated at low THP concentrations (70–350 ng/ml), resembling plasma concentrations, and at high THP concentrations (1.75–8.75 µg/ml), resembling urinary concentrations. Results. High (urinary) THP concentrations inhibited PMNL apoptosis and chemotaxis and stimulated PMNL phagocytosis, while low (plasma) THP concentrations increased PMNL chemotaxis. Conclusions. These data indicate that THP influences several PMNL functions, suggesting a crucial immunomodulatory role for this glycoprotein in host defence mechanisms of the kidney and genitourinary tract.
Thomas Wimmer; Gerald Cohen; Marcus D. Saemann; Walter H. Hörl. Effects of Tamm-Horsfall protein on polymorphonuclear leukocyte function. Nephrology Dialysis Transplantation 2004, 19, 2192 -2197.
AMA StyleThomas Wimmer, Gerald Cohen, Marcus D. Saemann, Walter H. Hörl. Effects of Tamm-Horsfall protein on polymorphonuclear leukocyte function. Nephrology Dialysis Transplantation. 2004; 19 (9):2192-2197.
Chicago/Turabian StyleThomas Wimmer; Gerald Cohen; Marcus D. Saemann; Walter H. Hörl. 2004. "Effects of Tamm-Horsfall protein on polymorphonuclear leukocyte function." Nephrology Dialysis Transplantation 19, no. 9: 2192-2197.
Gerald Cohen; Michael Rudnicki; Walter H. Hörl. Uremic toxins modulate the spontaneous apoptotic cell death and essential functions of neutrophils. Kidney International 2001, 59, 48 -52.
AMA StyleGerald Cohen, Michael Rudnicki, Walter H. Hörl. Uremic toxins modulate the spontaneous apoptotic cell death and essential functions of neutrophils. Kidney International. 2001; 59 (s78):48-52.
Chicago/Turabian StyleGerald Cohen; Michael Rudnicki; Walter H. Hörl. 2001. "Uremic toxins modulate the spontaneous apoptotic cell death and essential functions of neutrophils." Kidney International 59, no. s78: 48-52.
Gerald Cohen; Michael Rudnicki; Walter H. Hörl. Uremic toxins modulate the spontaneous apoptotic cell death and essential functions of neutrophils. Kidney International 2001, 59, 48 -52.
AMA StyleGerald Cohen, Michael Rudnicki, Walter H. Hörl. Uremic toxins modulate the spontaneous apoptotic cell death and essential functions of neutrophils. Kidney International. 2001; 59 (s78):48-52.
Chicago/Turabian StyleGerald Cohen; Michael Rudnicki; Walter H. Hörl. 2001. "Uremic toxins modulate the spontaneous apoptotic cell death and essential functions of neutrophils." Kidney International 59, no. s78: 48-52.